Ib qho kev piav qhia ntawm D7 Protein Structure Thiab Physiological Roles nyob rau hauv cov ntshav pub Nematocera Part 2
Jun 14, 2023
3.2. Biogenic Amine Binding D7s
Muaj ntau tshaj 460 hom Anopheles, muab faib ua 7 subgenera [56]. Txog tam sim no, cov genome ntawm 18 hom Anopheles (hais txog hom kab mob) tau ua tiav thiab muaj nyob rau hauv Vector Base, sawv cev rau peb lub ntsiab kev kho mob tseem ceeb subgenera ntawm Anopheles: Cellia, Anopheles, thiab Nyssorhynchus uas nyob hauv thaj chaw sib txawv hauv ntiaj teb thiab sib txawv los ntawm ib leeg mus txog rau 100 lab xyoo dhau los (raws li yog rooj plaub ntawm Cellia thiab Nyssorrhynchus) [57–59]. Anopheles sp yoov tshaj cum uas nws cov genomes tau tshaj tawm txog tam sim no (Daim duab 2) muaj 2–5 D7S (nyob ntawm subgenera thiab series), ntxiv rau yam tsawg kawg ob daim ntawv ntev (D7L2 thiab D7L3), thaum qee qhov muaj peb daim ntawv ntev (D7L1, tam sim no. hauv qee cov Cellia series thiab Anopheles subgenus) [29,60].
Lub genome yog ze ze rau kev tiv thaiv kab mob. Tib neeg genome muaj tag nrho cov noob uas xav tau rau lub cev tiv thaiv kab mob, suav nrog cov noob rau lub cev tiv thaiv kab mob, cov noob rau kab mob thiab kab mob, thiab lwm yam. Cov noob no muaj feem cuam tshuam nrog kev ua haujlwm ntawm lub cev tiv thaiv kab mob thiab cuam tshuam rau tib neeg kev tiv thaiv thiab kev tiv thaiv kab mob.
Ntxiv rau qhov no, qhov sib txawv ntawm cov genome kuj tuaj yeem cuam tshuam rau kev ua haujlwm thiab kev tiv thaiv ntawm lub cev. Muaj ntau ntau cov gene polymorphisms hauv tib neeg genome, uas txiav txim siab txog qib ntawm kev tiv thaiv kab mob hauv ntau haiv neeg. Piv txwv li, tib neeg leukocyte antigen (HLA) yog cov noob tseem ceeb hauv lub cev tiv thaiv kab mob, thiab nws cov polymorphism tso cai rau tib neeg los tsim cov kab mob sib txawv thiab kev tiv thaiv.
Nyob rau hauv xyoo tas los no, nrog rau kev sib sib zog nqus ntawm kev tshawb fawb genomics, ntau thiab ntau cov kev tshawb fawb tau pom tias genomic variation yog ze ze rau qhov tshwm sim ntawm ntau yam kab mob tiv thaiv kab mob. Piv txwv li, cov kab mob autoimmune (xws li lupus, rheumatoid mob caj dab, ntau yam sclerosis, thiab lwm yam) thiab cov kab mob tiv thaiv kab mob (xws li AIDS, mob npaws, thiab qhov ncauj qhov ntswg, thiab lwm yam) yog txhua yam cuam tshuam nrog kev hloov pauv ntawm genomic.
Yog li ntawd, kev tshawb fawb genome yog qhov tseem ceeb rau kev nkag siab txog kev ua haujlwm ntawm lub cev tiv thaiv kab mob, cov txheej txheem ntawm tus kab mob, thiab kev kho tus kheej rau cov neeg sib txawv. Los ntawm qhov kev xav no, peb yuav tsum txhim kho kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv zoo. Cistanche yog nplua nuj nyob rau hauv ntau yam tshuaj antioxidant, xws li vitamin C, vitamins, carotenoids, thiab lwm yam. Cov khoom xyaw no tuaj yeem tshem tawm cov dawb radicals, txo oxidative kev nyuaj siab, thiab txhim kho kev tiv thaiv. tiv thaiv kab mob.
Nyem cistanche tubulosa cov txiaj ntsig
Ob peb xyoos tom qab Hamadarin tus cwj pwm, 5 D7rs (D7r1-D7r5) uas nws cov ntawv sau tseg yav dhau los tau pom hauv Anopheles gambiae (Cellia) poj niam cov qog ntshav [27,32] tau cim [34]. Tag nrho cov ntawm lawv, tshwj tsis yog D7r5, tau tshaj tawm los khi serotonin nrog kev sib koom siab heev (kev sib cais tsis tu ncua, KD, qis dua 3 nM) nrog rau cov tshuaj histamine nrog KD txij li 41 txog 111 nM. Xav paub ntau ntxiv, tab sis tsis yog qhov xav tsis thoob lawv lub peev xwm los khi lwm yam biogenic amines thiab lawv cov kev sib raug zoo rau lawv kuj yog qhov txawv (cov ntsiab lus hauv Table 1), qhia txog kev sib txawv ntawm kev ua haujlwm ntawm cov tswv cuab sib txawv ntawm tsev neeg D7, txawm nyob hauv tib hom. Nyob rau hauv txhua rooj plaub, qhov kev sib khi stoichiometry yog 1: 1, thiab kev sib tw kev sib tw tau pom tias biogenic amines qhia tib qhov chaw sib khi [34], tom qab tau lees paub los ntawm cov qauv siv lead ua ntawm Anopheles gambiae D7r4 khi rau serotonin thiab lwm yam biogenic amines [28] .
Orthology ntawm An. gambiae D7rs muaj nyob rau hauv tag nrho cov Anophelines soj ntsuam hom, uas nws genomes yog annotated nyob rau hauv Vector Base kom deb li deb (Daim duab 2), txawm hais tias ib co poob ib tug los yog ntau tus tswv cuab [29,60]. Txawm hais tias qhov sib txawv ntawm cov kab ke thoob plaws ntau hom thiab pab pawg, cov seem tseem ceeb ntawm cov kab mob biogenic amines, txheeb xyuas ua tsaug rau Anopheles gambiae D7r4 cov ntaub ntawv qauv [28], tau txais txiaj ntsig zoo heev hauv kev xyaum txhua D7r1-D7r4 cov ntaub ntawv thoob plaws hom. rau subgenera Cellia, Nissorhynchus, thiab Anopheles, qhia tias lawv txhua tus tuav lub peev xwm los khi serotonin [29]. Ntawm qhov tod tes, txhua hom D7r5 qhia txog kev hloov pauv hauv ntau yam tseem ceeb seem [29] qhia tias raws li kev soj ntsuam rau Anopheles gambiae D7r5 [34], lawv poob lub peev xwm los khi ib qho biogenic amine.
Curiously, thaum Anopheline D7S cov ntaub ntawv zoo li muaj feem ntau khaws cia lawv cov biogenic amine binding muaj peev xwm, qhov no tsis muaj tseeb rau cov ntaub ntawv ntev, qhov ntau ntawm kev hloov pauv, neo-functionalization, thiab poob ntawm kev ua haujlwm raug pom nyob thoob plaws cov hom sib txawv. subgenera.
Thawj Anopheles D7L los ua tus cwj pwm, lub npe hu ua Anopheles stephensi D7L1 (AnSt-D7L1), tam sim no suav tias yog D7L2 vim nws qhov zoo sib xws rau An. gambiae cov ntaub ntawv tau pom tias tsis tuaj yeem khi serotonin lossis ib qho bioogenic amines kuaj tab sis khi eicosanoids hauv nws N-terminal domain [30]. Zoo li Anopheles gambiae, An. Stephensi belongs rau subgenus Cellia. Txawm li cas los xij, tsis ntev los no D7L cov tswv cuab koom nrog lwm tus Anopheline subgenera An. atroparvus D7L1 (Anopheles) thiab An. darling D7L2 (Nyssorhynchus) tau pom tias khi serotonin nrog kev sib raug zoo siab heev (hauv lawv C-terminal domain) [29], nthuav tawm KDs piv rau cov pom rau Anopheles gambiae luv daim ntawv [34] thiab Aedes ntev daim ntawv [34,37,38 ]. Txawm li cas los xij, feem ntau, lawv lub peev xwm los khi lwm yam biogenic amines tsis tuaj lossis qis dua. Qhov tsis muaj peev xwm los khi serotonin pom hauv An. stephensi tuaj yeem nkag siab zoo dua ua tsaug rau cov ntaub ntawv qauv [30].
Nyob rau hauv Anopheline yoov tshaj cum, D7S (los yog D7r) cov proteins ua ke mus rau C-terminal domain ntawm Anopheles thiab Aedes D7L, thiab X-ray crystallography cov kev tshawb fawb tau lees paub tias D7S proteins thiab OBP-zoo li C-terminal domain ntawm biogenic amine khi D7L yog qhov zoo sib xws. (28,29,36]. Raws li tus yam ntxwv dav dav, serotonin / biogenic amine binding hnab tshos yog ib qho kab noj hniav hydrophobic lined nrog cov ntxhiab tsw, ncig los ntawm 8 a-helices uas ruaj khov los ntawm 3 disulfide bonds (Figures 1B thiab 3). muaj qee cov polar charged residues nyob rau hauv nkag ntawm lub hnab tshos (glutamic thiab aspartic acids) tso cai rau hydrogen bonds nrog aliphatic ib feem ntawm serotonin (Daim duab 3 thiab 4). Lub ligand yog ntxiv stabilized los ntawm ib tug hydrogen daim ntawv cog lus tsim ntawm nws cov pab pawg neeg indole thiab ib. tyrosine (lyr 94 nyob rau hauv An. gambiaeD7r4 Daim duab 3). Cov residues paub tias tseem ceeb rau serotonin/biogenic amine binding yog highlighted nyob rau hauv grey thawv nyob rau hauv daim duab 4. Qhov kev sib raug zoo qhia tau hais tias feem ntau ntawm lawv yog kev txuag, txawm tias qhov sib txawv ntawm lwm cov residues, txawm nyob rau hauv cov proteins qhia tsis khi biogenic amines, zoo li An. stephensi D7L1, qhov twg qhov poob ntawm kev khi yog vim qee qhov kev hloov pauv residue (Daim duab 4).
Hauv qee cov proteins, serotonin 5- pab pawg hydroxyl tsim ib daim ntawv cog lus hydrogen nrog histidine (Daim duab 3 thiab 4 tseem ceeb nrog lub thawv xiav) raws li pom hauv D7r4 thiab Aedes aegypti D7L1 (Nws 35 hauv thawj zaug thiab Nws 189 nyob rau hauv thib ob). Qhov no Nws yog hloov pauv los ntawm alanine (Ala-190) hauv An-StD7L1, tab sis qhov no yuav tsis txaus los piav qhia qhov poob ntawm kev ua haujlwm, txij li An. darlingi D7L2 (subgenus Nyssorhynchus) thiab An. iteroparous D7L1 (subgenus Anopheles) khi serotonin txawm tias qhov no Nws yog hloov los ntawm methionine lossis alanine, raws li [29]. Yog li ntawd, qhov sib txawv tseem ceeb ntawm qhov txawv ntawm Anopheles stephensi D7L1 los ntawm yoov tshaj cum D7s uas khi serotonin yog qhov poob ntawm qhov thib ob thiab qhov kawg cysteine hauv lawv C-terminal domain (cov thawv ntsuab thiab liab C-terminal sau, Daim duab 4). Ob qhov seem no yuav tsim qhov thib ob disulfide daim ntawv cog lus ntawm C-terminal, plaub ntawm tag nrho cov protein, yog li sau npe tias DS4. Nyob rau hauv lawv qhov tsis tuaj yeem muaj kev hloov pauv ntawm helix H2 thiab unwinding ntawm helix B2, vim li ntawd, W173, uas los ntawm txoj kev tsis muaj nyob rau hauv biogenic amine binding D7s, thiab R177 (AnSt-D7L1) occupies ib feem ntawm lub hnab ris, piav qhia. nws tsis muaj peev xwm los khi biogenic amines, raws li qhia thiab sib tham hauv kev nthuav dav yav dhau los [30].
Qhov tsis tuaj ntawm ob cysteine yog tseem pom nyob rau hauv tag nrho D7L1s thiab D7L2s qhia nyob rau hauv tag nrho cov hom ntawm subgenus Cellia ua rau lub tswv yim hais tias lawv yuav tau poob lub biogenic amine binding muaj nuj nqi ib yam nkaus thiab [29]. Qhov kev xav no tau txhawb ntxiv los ntawm kev soj ntsuam ntawm lawv cov qauv, tsim siv AlphaFold [61] (Daim duab 5). Zoo li qhov pom kev sim rau An. stephensi D7L1 [30], qhov tsis muaj DS4 hauv Cellia D7L1 thiab D7L2 cov proteins yog nrog los ntawm kev hloov pauv hauv helix H2 txoj hauj lwm thiab lwm yam kev hloov kho uas ua rau lub hnab tshos C-terminal bulkier nrog cov residues nyob ib feem ntawm cov kab noj hniav tsis tawm qhov chaw txaus rau haum serotonin lossis lwm yam biogenic amines (Daim duab 5). Ntawm qhov tod tes, qhov degree ntawm unwinding nyob rau hauv helix B2 pom nyob ntawm cov hom los yog tej zaum yuav tshwm sim los ntawm ib tug ntau unstable helix hloov ntawm ib lub xeev mus rau lwm yam.
Lwm pab pawg ntawm cov ntawv ntev yog D7L3, tam sim no nyob rau hauv tag nrho cov Anopheles hom uas muaj genomes txog tam sim no. Anopheles gambiae D7L3 khi serotonin nrog siab affinity thiab tshwj xeeb [29], thiab nws C-terminal domain muaj tag nrho cov tseem ceeb amino acids qhia tau hais tias muaj kev koom tes nyob rau hauv biogenic amine kev sib cuam tshuam [28] txuag (Daim duab 4) thiab nrog tib spatial disposition li D7r4. [29]. Qhov kev txuag no kuj tau pom nyob rau hauv tag nrho D7L3s soj ntsuam los ntawm Anopheles hom, tsis hais cov subgenera, qhia tias daim ntawv no, uas nyob rau hauv ib qho chaw nyob ib sab mus rau cov ntawv luv luv hauv pawg D7, khaws cia txoj haujlwm no hauv txhua hom [29].
Hauv Culicinae yoov tshaj cum, D7S orthologs thiab 2 D7Ls (D7L1 thiab D7L2) kuj pom. Txawm li cas los xij, tsis zoo li qhov pom hauv Anophelinae, lawv cov ntawv luv luv tsis khi biogenic amines raws li cov txiaj ntsig tau tshaj tawm rau Aedes aegypti (AeD7S1) thiab Culex quinquefasciatus (D7CQS1) [29], thaum lawv cov ntaub ntawv ntev tau pom zoo kom deb li deb, tshwj tsis yog Culex. quinquefasciatus D7L1, muaj kev sib raug zoo heev rau cov ligands (tshwj xeeb tshaj yog serotonin) raws li qhia rau Aedes aegypti D7L1 (yav tas los hu ua AeD7L) thiab D7L2 [34,37], Ae. albopictus (D7L1) [38] thiab Culex quinquefasciatus (CxD7L2) [39]. Cov ntaub ntawv tsim qauv qhia tias kev poob haujlwm hauv lawv cov ntawv luv luv, txawm hais tias muaj tag nrho 6 qhov kev khaws cia cysteines thiab tau tsim los ntawm -helices, yog vim qhov luv luv hauv lawv cov C-terminal tsis muaj -helix H2 cheeb tsam, thiab qhov sib txawv ntawm -helices. cov txheej txheem uas ua rau txhaws ntawm lub hnab ris [29] Tseem ceeb heev, culicines tsis muaj D7L3, daim ntawv ntev uas nyob rau hauv Anopheles sp. lies tam sim ntawd nyob ib sab ntawm cov ntawv luv luv hauv lub cassette, thiab feem ntau ntawm DS (D7r1–r4) hauv Anopheles, khi serotonin [29].
Biogenic amines yog cov neeg kho kom haum xeeb ntawm ntau cov txheej txheem koom nrog hauv cov lus teb rau cov leeg nqaij, ntau zaus cuam tshuam lawv [6,62]. Histamine, piv txwv li, yog lub zog nruab nrab ntawm cov kab mob thiab kev ua xua thiab tso tawm los ntawm mast cell degranulation. Nws activates lub endothelium, nce vascular permeability, thiab txhawb khaus thiab mob [63-67]. Nws kuj tseem paub los txhawb cov leeg nqaij leeg. Serotonin thiab norepinephrine tso tawm sai sai los ntawm cov platelets thiab neutrophils yog agonists ntawm platelet aggregation thiab vasoconstriction. Serotonin tseem koom nrog hauv inflammatory teb los ntawm activating endothelium thiab txhawb khaus thiab mob [6]. Qhov ua tau zoo thiab qhov tseem ceeb ntawm cov D7s rau vector biology tau pom los ntawm lawv lub peev xwm los cuam tshuam cov leeg nqaij leeg [34,37] raug ntxias los ntawm cov biogenic amines sib txawv thiab cuam tshuam nrog serotonin-mediated platelet activation [38].
3.3. Eicosanoid Binding D7s (N-Terminal Domain ntawm D7Ls)
Qhov tseeb tias D7L daim ntawv muaj ob hom OBP zoo li tau tsa qhov muaj peev xwm tias cov proteins no tuaj yeem muaj lwm cov ligands hauv lawv cov N-terminal domain. Xwb, Ae. aegypti D7L1, paub los khi biogenic amines [34], yog thawj daim ntawv ntev qhia tau khi cystyl leukotrienes (CysLTs) thiab leukotriene B4 (LTB4) los ntawm nws cov N-terminal [36]. Tsis ntev tom qab, An. stephensi D7L1 (AnSt-D7L1), uas tsis khi biogenic amines lossis lwm yam ligand kuaj hauv nws C-terminal sau, tau pom tias khi tsis yog CysLTs nrog kev sib raug zoo siab heev tab sis kuj thromboxane A2 (TXA2) analogs (U46619 thiab carbocyclic thromboxane. ) [30] ib. Isothermal titration calorimetry (ITC) kev soj ntsuam thiab cov ntaub ntawv qhia tau hais tias ob leeg ligands sib koom tsawg kawg yog ib feem ntawm qhov chaw khi nyob rau hauv nws lub N-terminal domain [30].
Lwm cov D7L1 thiab L2 proteins nyob rau hauv Culicinae thiab Anophelinae yoov tshaj cum kuj tau pom los khi eicosanoids, tab sis nrog sib txawv affinities thiab tshwj xeeb, ntxiv rau lawv lub peev xwm los khi serotonin. Hauv Culicinae (Ae. aegypti D7L2 [37], Ae. albopictus D7L1 [38], thiab Cu. quinquefasciatus D7L2 [39]) tau pom tias khi CysLTs thiab LTB4 (tom kawg nkaus hauv Aedes), tab sis nrog affinities ho qis dua li qhia. rau Ae. ua d7l1. Interestingly, lawv tau txais lub peev xwm los khi U46619. Hauv Anophelinee yoov tshaj cum. Ib. iteroparous D7L1 (Anopheles) khi CysLTs, tab sis nrog qis affinity, thaum An. darling D7L2 (Nyssorhynchus) khi CysLTs nrog siab affinity thiab TXA2 analogs (U46619) [29]. Cov D7s cov proteins no yog ob qho kev ua haujlwm vim lawv kuj khi serotonin.
Kev sib piv ntawm kev khi qhov chaw seem ntawm ligand complex crystals los ntawm An. darlingi D7L2, ib. Stephensi D7L1 thiab Ae. aegypti D7L1 [29,30,36] tau qhib txoj haujlwm tseem ceeb ntawm cov khoom seem rau eicosanoid khi ntawm N-terminal domain (qhov tseem ceeb hauv daim duab 4). Qhov tseem ceeb tshwj xeeb rau kev ruaj khov ntawm cov ligands yog Trp-37, Trp-40, thiab Tyr-52 (AnSt-D7L1 raws li siv), thiab thaum tom kawg yog hloov los ntawm Phe (daj arrowhead Daim duab 4), raws li pom hauv Ae. aegypti D7L1, lub peev xwm los khi TXA2 ntxiv rau CysLTs ploj lawm. Qhov tseem ceeb sib npaug yog qhov muaj Lys -152 tsim ib daim ntawv cog lus hydrogen lossis ntsev choj nrog cov carboxyl ntawm eicosanoid. Ntau qhov tseem ceeb ntawm cov seem no tau khaws cia hauv D7L1s thiab D7L2, tshwj xeeb tshaj yog nyob rau tom kawg, tam sim no nyob rau hauv lwm hom Anophelinae tshuaj ntsuam xyuas, tawm tswv yim tias tsis hais cov sub-genus lawv tau khaws tsawg kawg ib daim ntawv ntev (D7L1 thiab / lossis D7L2) muaj peev xwm los khi cysteyl leukotrienes [29], raws li tau qhia tsis ntev los no los ua cov ntaub ntawv ntawm Anopheles gambiae D7L1 thiab D7L2 [68]. Ob tug An. gambiae D7Ls tsis tuaj yeem khi biogenic amines tab sis khaws lub peev xwm los khi eicosanoids [68], tsis yog qhov xav tsis thoob vim lawv qhov zoo sib xws (tshwj xeeb D7L2 daim ntawv) rau yav dhau los piav txog Anopheles stephensi D7L1 (tam sim no L2) [30] thiab tias ob hom yog subgenus. Cellia thiab lawv D7L1 thiab L2 tsis muaj DS4 ntawm C-terminal domain.
Qhov tseem ceeb, thaum D7L3s muaj nyob rau hauv tag nrho cov Anopheles hom thiab muaj lawv cov residues txuas mus rau serotonin khi ntawm C-terminal tsis tshua muaj kev txuag, N-terminal ntawm txhua hom tau kwv yees tias yuav tsis tuaj yeem khi eicosanoids vim muaj kev hloov pauv tseem ceeb hauv cov seem uas paub txog. ua qhov tseem ceeb rau txoj haujlwm no. Qhov kev xav no tau lees paub sim thaum ITC tau pom tias An. gambiae D7L3 tsis khi ib qho eicosanoid kuaj [29].
Txaus siab heev, D7L cov ntaub ntawv kuj muaj nyob rau hauv cov xuab zeb yoov (tsev neeg: Psychodidae) [17,69] txawm tias qhov kev ncua deb ntawm lawv thiab yoov tshaj cum (Culicidae). Cov ntaub ntawv ntev uas muaj cov qaub ncaug ntawm ob hom phlebotomus (P. papatasi thiab P. duboscqi) khaws lub peev xwm los khi CysLTs nrog cov affinities siab heev thiab TXA2 analogs [40]. Cov ntaub ntawv uas tau txais los ntawm P. papatasi D7L1 tau pom tias eicosanoid khi tau tshwm sim kuj nyob rau hauv N-terminal, zoo ib yam li tau piav qhia rau yoov tshaj cum 'D7L, thaum nws C-terminal luv luv thiab truncated, yog li tsis tuaj yeem khi biogenic amines [ 40].
Kev soj ntsuam ntawm pob txha pob txha qhia tias thawj Diptera tau tshwm sim hauv Triassic, ntau dua 240 lab xyoo dhau los (MYA). Thaum kawg ntawm Triassic, Culicomorpha, thiab Psychodomorpha infra txiav txim tau tshwm sim, txhais tau hais tias yoov tshaj cum thiab xuab zeb yoov kab sib txawv ntau dua 200 MYA, feem ntau yuav los ntawm cov poj koob yawm txwv phytophagous, qhia tias lawv tsim tus cwj pwm los noj ntshav ntawm nws tus kheej [5,70 ]. Qhov no tau txais kev txhawb nqa los ntawm qhov tseeb tias feem ntau ntawm cov tsev neeg salivary gland protein uas tsuas yog pom hauv Nematocera yog qhov sib txawv ntawm Psychodidae thiab Culicidae tsev neeg, lub ntsiab lus uas nyuaj heev los muab orthologs ntawm lawv [5]. Yog li ntawd, yoov tshaj cum thiab sandfly D7Ls, tej zaum yog los ntawm nws tus kheej los ntawm ib tug zoo xws li los yog ib tug poj koob yawm txwv gene, tej zaum yuav coding rau ib tug OBP, uas yog tom qab recruited ntawm nws tus kheej mus rau lawv sialome thiab tau txais lub luag hauj lwm los ntawm convergent evolution. Qhov kev xav no tau txhawb ntxiv los ntawm kev soj ntsuam tias lawv muaj cov qauv sib txawv intron / exon [40].
Qhov tsis muaj D7S orthologs hauv cov xuab zeb yoov thiab qhov tsis muaj peev xwm ntawm lawv cov D7L orthologs los khi biogenic amines tsis txhais hais tias lawv cov qaub ncaug tsis muaj molecules rau sequester cov hom phiaj. Tseeb, nyob rau hauv cov xuab zeb ya qaub ncaug lwm tsev neeg protein "Daj" tau coj txoj haujlwm los khi biogenic amines [71], thaum lwm tsev neeg ntawm OBP-zoo li protein PdSP15 pom nyob rau hauv lawv cov qaub ncaug ua los ntawm inhibiting kev sib cuag txoj kev ua kom [41]. Qhov no yog ib qho piv txwv zoo ntawm yuav ua li cas kev ywj pheej evolution ua rau cov repertoires sib txawv ntawm cov proteins tsom rau tib lub molecules.
Leukotrienes (CysLTs thiab LTB4) yog cov muaj zog o thiab kev tsis haum tshuaj kho mob zais cia los ntawm cov kab mob mast thiab lwm cov kab mob tiv thaiv kab mob xws li eosinophils thiab macrophages, nrog rau cov hlwb epithelial thiab endothelial [72]. CysLTs raug tso tawm raws li cov lus teb rau yoov tshaj cum tom ua ke nrog histamine [62], ua rau muaj zog vascular permeability nyob rau hauv daim tawv nqaij [63] thiab ua rau erythema thiab wheal tsim [73,74], thaum LTB4 yog lub npe hu ua chemoattractant lub luag hauj lwm rau kev nyiam lub cev tiv thaiv kab mob. mus rau qhov chaw teb [72] Lub peev xwm los khi cov neeg muaj zog tiv thaiv kab mob no yuav yog ib qho tseem ceeb rau inhibit endothelium activation, edema tsim, tiv thaiv cell infiltration, khaus, thiab mob tshwm sim los ntawm cov eicosanoids, yog li tiv thaiv los yog ncua sij hawm tus tswv tsev paub thiab cia cov kab no noj ntshav. Cov tshuaj tiv thaiv kab mob no tau pom hauv cov qauv nas thaum txhaj tshuaj Ae. albopictus D7L1 (uas khi LTB4, CysLTS, thiab biogenic amines, ntxiv rau qhov tsis tshua muaj affinity rau U46619) 10 min ua ntej pro-inflammatory kev sib tw nrog -glucan los ntawm Saccharomyces cerevisiae txo cov kab mob tiv thaiv kab mob nkag mus rau hauv peritoneal kab noj hniav [38].
Thromboxane A2 yog tsim thiab secreted los ntawm activated platelets nyob rau hauv teb rau collagen raug. Nws ces khi rau nws cov receptors tam sim no ntawm platelet nto propagating platelet activation thiab potentiating aggregation [75,76]. Tseem ceeb heev, ntxiv rau TXA2 platelets tseem zais lwm cov pro-hemostatic thiab pro-inflammatory molecules, xws li ADP, serotonin, polyphosphate, thiab norepinephrine [6]. TXA2 kuj txhawb nqa vasoconstriction [77,78] thiab tsis ntev los no tau pom tias ua rau khaus thiab khawb cov lus teb hauv nas [79,80].
Ob peb D7Ls tau pom tias khi U46619, qhov ruaj khov TXA2 analogue los ntawm ITC kev sim thiab pom tias inhibit platelet aggregation hauv vitro induced los ntawm U46619. Qhov tseem ceeb, cov proteins no kuj inhibit platelet aggregation induced los ntawm arachidonic acid (thromboxane A2 precursor) thiab qis concentrations ntawm collagen (nyob rau hauv uas platelet aggregation cia siab rau TXA2 thiab ADP rau potentiate lub teeb liab), ua pov thawj tias lawv muaj peev xwm khi platelet synthesized TXA2, thiab tsis tsuas yog nws ruaj khov analog siv rau ITC thiab crystallography thwmsim [29,30,37,38,40].
CysLTs thiab TXA2 kuj paub los txhawb cov leeg nqaij leeg. Kev ntsuam xyuas tau qhia tias An. stephensi D7L1 (tam sim no muab faib ua D7L2), piv txwv li, muaj peev xwm inhibit LTC4- txhawb nqa guinea pig ileum contraction thiab U46619- txhawb nqa nas aorta contraction hauv vivo [30].
Kab OBPs tau pib piav qhia nyob rau hauv olfactory thiab gustatory appendages, qhov chaw uas lawv yuav khi, solubilize, thiab thauj semiochemicals, nrog rau tswj lub sij hawm ntawm odorant teb. Tom qab ntawd lawv tau pom tias muaj nyob rau hauv lub cev tsis hnov tsw, xws li midgut, cov qog nqaij hlav, cov qog nqaij hlav, cov kab mob hauv lub cev, Malpighian tubules, thiab txawm nyob rau hauv lub caj pas venom, qhia tias lawv yuav muaj ntau yam ligands thiab lawv cov dej num. tsis txwv rau chemoreception (saib hauv [20,21]). Yog li ntawd, feem ntau ntawm cov kev txheeb xyuas thiab cov qauv ntaub ntawv muaj tau ua nrog ligands xws li pheromones, tsw molecules, cawv, thiab lwm yam hluavtaws organic tebchaw [20,26,81–84]. Tsis muaj kab OBP tau pom los khi biogenic amines txog tam sim no. Txawm li cas los xij, qee qhov OBPs tau pom tias khi ntev-chain fatty alcohols, xws li bombykol, ib qho pheromone uas tsim los ntawm Bombyx mori [82], los yog ntev-chain fatty acids thiab arachidonic acid, lub precursor ntawm eicosanoids raws li qhia rau Aedes aegypti OBP22 [85, 86], piv txwv. Ae. aegypti OBP22 yog tam sim no nyob rau hauv lub kav hlau txais xov, poj niam proboscis, thiab txiv neej lub cev xeeb tub thiab raug xa mus rau cov poj niam thaum lub sij hawm mating [{14}}], hais tias nws muaj nuj nqi yog tsis txwv rau chemoreception. Cov qauv kev tshawb fawb pom tau tias nyob rau hauv lub xeev tsis muaj ligand, cov protein no yog tsim los ntawm 6 -helices xws li kab classical OBPs. Txawm li cas los xij, nyob rau hauv lub xub ntiag ntawm ligand, OBP22 tau txais kev hloov pauv hauv nws lub C-qhov dav hlau uas ua rau lub xya-helix [85] ua kom lub hnab ntim khoom loj. Qhov tsim nyog, cov kws sau ntawv tau pom tias qhov OBP no muaj qhov zoo sib xws rau N-terminal domain ntawm D7L cov proteins, thiab nws lub xya helix tsim los ntawm kev khi rau fatty acids nyob rau hauv txoj hauj lwm zoo sib xws rau lub xya helix pom hauv cov D7L lipid-binding domains [85 ].
3.4. ADP Binding D7s
Culex quinquefasciatus D7L1 (CxD7L1), txawv ntawm ib qho D7L tus yam ntxwv kom deb li deb tsis tuaj yeem khi eicosanoids lossis biogenic amines, tej zaum vim yog qee qhov kev hloov pauv tseem ceeb hauv qee txoj haujlwm tseem ceeb ntawm lawv cov hnab ris N- thiab C-terminal, xws li muaj cov glycine. es tsis txhob ntawm glutamic acid nyob rau hauv txoj hauj lwm 155, uas yog ib qho tseem ceeb heev los tsim ib tug hydrogen daim ntawv cog lus nrog cov 5-hydroxyl pab pawg neeg ntawm serotonin indole nplhaib nyob rau hauv feem ntau ntawm biogenic amine khi D7s, raws li zoo raws li ib tug histidine ntawm txoj hauj lwm 172 es tsis txhob. tyrosine, raws li pom nyob rau hauv feem ntau ntawm biogenic amine-binding D7 proteins (Daim duab 4). Hloov chaw, nws tau pom tias khi adenosine phosphorylated derivatives ATP, ADP, thiab AMP (50adenosine tri-, di, thiab mono diphosphate, ntsig txog) nrog kev sib raug zoo, adenosine, thiab adenine nrog qis affinities [39]. Lwm qhov peculiarity yog qhov tseeb tias kev sib cuam tshuam nrog nws cov ligands tshwm sim ntawm N- thiab C-terminal OBP-zoo li domains, tsis yog kab noj hniav hauv ib qho ntawm lawv [39].
ATP thiab ADP intracellular concentrations yog nruj me ntsis tswj thiab thaum muaj kev raug mob, ADP thiab ATP raug tso tawm nyob rau hauv lub extracellular milieu tom qab cell lysis thiab muaj peev xwm ua raws li pro-inflammatory thiab pro-hemostatic molecules [76,87]. ADP activates platelet aggregation thiab yog secreted los ntawm activated platelets nyob rau hauv cov lus teb rau agonists, xws li collagen raug tom qab vascular raug mob, mus rau propagate aggregation ntxiv [76,88]. Vim nws lub peev xwm los khi ADP, CxD7L1 [39] tau pom tias inhibit platelet zoo hloov vim qhov qis qis ntawm collagen, nrog rau kev sib sau ua ke los ntawm cov koob tshuaj ntau dua (1 µM) ntawm ADP thiab qis dua ntawm collagen nyob rau hauv uas aggregation nyob ntawm kev tso tawm ntawm ob tus neeg nruab nrab xws li ADP thiab TXA2.
4. Mosquito Juvenile Hormone-Binding Protein (mJHBP): Dab tsi yog D7-zoo li Protein Ua hauv Mosquito Hemolymph?
Xyoo 2017 Kim thiab cov npoj yaig [89], txhawm rau nrhiav D7-cov proteins uas muaj feem cuam tshuam sab nraud cov qog qaub ncaug, pom thiab piav qhia txog cov protein tshiab uas feem ntau muaj nyob rau hauv hemolymph ntawm pupae thiab cov neeg laus (txiv neej thiab poj niam) Aedes aegypti yoov tshaj cum. Orthologues ntawm cov protein no kuj pom muaj nyob rau hauv txawv Anopheles thiab Culex hom, sib koom ntau zoo sib xws tshaj li lawv salivary D7 proteins. Zoo li salivary D7 cov ntaub ntawv ntev, cov protein no muaj ob hom OBP zoo li. Nws yog N-terminal khaws cia ntau ntawm cov seem uas pom tias muaj kev koom tes hauv eicosanoid khi hauv salivary D7s, qhia tias lub hnab ntim lipid tuaj yeem tshwm sim, thaum nws cov C-terminal muaj pes tsawg leeg sib txawv ntawm lwm yam D7 / D7-zoo li piav txog tam sim no. ITC cov kev sim tau pom tias cov protein no, hu ua yoov tshaj cum Juvenile Hormone-Binding Protein (mJHBP), tsis tuaj yeem khi eicosanoids tab sis muaj kev sib raug zoo thiab tshwj xeeb rau cov menyuam yaus (JH). Cov ntaub ntawv qauv qhia tau hais tias qhov tseeb nws qhov N-terminal domain architecture zoo ib yam li lawv cov sib koom ua ke hauv D7L cov proteins, muaj ob daim ntawv cog lus disulfide thiab yog tsim los ntawm 7 -helices thiab muaj feem ntau ntawm cov seem uas cuam tshuam nrog JH III. Txawm li cas los xij, qhov sib txawv ntawm cov tau pom rau salivary D7L cov proteins uas tau piav qhia txog tam sim no, qee qhov C-terminal residues kuj koom nrog hauv kev khi, tshwj xeeb tshaj yog qhov txuas ntxiv ntawm helix -13 kaw qhov nkag ntawm lub hnab ntawv khi [89]. Tseem ceeb heev, raws li tau hais los ntawm cov kws sau ntawv, cov protein no yog qhov sib txawv kiag li ntawm hemolymph juvenile hormone binding protein tau piav qhia txog tam sim no hauv Bombyx mori [90].
Cov menyuam yaus cov tshuaj tswj hwm cov txheej txheem ntau yam hauv kab nrog rau kev loj hlob [91], molting thiab metamorphosis [92], kev loj hlob thiab oogenesis [93-95], thiab kev tiv thaiv kab mob [96,97]. Thaum lub physiological lub luag hauj lwm ntawm Aedes aegypti mJHBP tau kawm los ntawm khob nws cov noob tawm los ntawm CRISPR-cas9, tsis muaj kev cuam tshuam rau kev loj hlob, kev loj hlob, los yog kev yug me nyuam [98]. Txawm li cas los xij, cov yoov tshaj cum tawm (KO) tau ua rau lub cev tsis muaj zog tiv thaiv kab mob, ua rau muaj kev cuam tshuam ntau dua rau cov kab mob kis tau zoo thaum sib tw nrog cov tshuaj sublethal ntawm E. coli thiab tsim cov tshuaj tua kab mob qis dua tom qab kis kab mob thaum piv rau cov yoov tshaj cum (WT) yoov tshaj cum. . Cov teebmeem no tau ua raws li tus lej qis thiab sib txawv ntawm hemocytes hauv KO yoov tshaj cum pom los ntawm cov kws sau ntawv [98].
5. Cov lus xaus
Salivary OBP-zoo li cov proteins, zoo li D7 thiab PdSP15 cov neeg hauv tsev neeg, ua lub luag haujlwm tseem ceeb hauv kev pab txhawb kev noj ntshav, tsom rau cov khoom sib txawv uas koom nrog hauv tus tswv tsev hemostasis thiab inflammatory teb. Gene duplication ntawm salivary genes, suav nrog D7s, thiab kev hloov pauv sai ua rau qhov nce thiab poob ntawm kev ua haujlwm hauv tsev neeg sib txawv. Qhov kev sib txawv no tsis yog tshwj xeeb rau D7 proteins thiab tau piav qhia hauv lwm tsev neeg xws li kab lipocalins [6,7].
Tus tswv tsev tiv thaiv tom qab tsis yog tshwj xeeb rau hematophagous Diptera, tsis yog lub hom phiaj lossis muaj cov proteins los daws lawv. Txawm li cas los xij, txoj hauv kev los daws cov teeb meem no muaj ntau haiv neeg ntawm pawg arthropods vim muaj kev ywj pheej ntawm kev hloov pauv ntawm hematophagy uas ua rau muaj ntau cov proteins los tiv thaiv tus tswv tsev hemostatic, inflammatory, thiab tiv thaiv kab mob [2,4,5,7,15,16] . Piv txwv li, D7 proteins tuaj yeem khi biogenic amines thiab eicosanoids. Nyob rau hauv cov zuam thiab cov kab mob triatomine lipocalins (kev ywj pheej evolution), ib tsev neeg muaj protein ntau sib txawv nrog cov qauv sib txawv heev uas muaj li ntawm 8 antiparallel -cov ntawv nyob ib puag ncig ib lub hnab khi, tuav cov haujlwm no [7,99–105]. Hauv cov xuab zeb yoov, daim ntawv luv luv D7s tsis tuaj, thiab biogenic amine binding muaj nuj nqi yog coj los ntawm "daj" protein tsev neeg [71], thaum lawv muaj D7Ls uas khi eicosanoids [40].
Culex quinquefasciatus D7L1, txawv ntawm lwm yam D7s, khi ADP. Apyrases, enzymes uas catalyze hydrolysis ntawm ATP thiab ADP rau AMP thiab Pi (inorganic phosphate) nrog rau ADP losis tswvyim dabtsi proteins thiab 50nucleotidases tau piav nyob rau hauv cov qaub ncaug ntawm ntau hom hematophagous arthropods hom, tsis hais txog lwm cov proteins uas inhibit platelet aggleculation. xws li collagen thiab thrombin (saib xyuas los ntawm [76]).
Kev nkag siab txog cov qaub ncaug yog qhov tseem ceeb rau kev kawm txog vector biology thiab nws cov kev cuam tshuam nrog tus tswv tsev. Tsis tas li ntawd, nws muab cov ntaub ntawv tseem ceeb rau kev txhim kho cov kab mob kab mob uas muaj kab mob tshiab. Piv txwv li, nyob rau hauv feem ntau cov kab mob vector-borne tus kab mob yog txhaj rau hauv tus tswv tsev ua ke nrog vector qaub ncaug thaum lub sij hawm tom. Qhov tseeb hais tias qee cov salivary proteins yog immunogenic, ua rau lawv zoo heev epidemiological cov cuab yeej ua biomarkers rau tib neeg raug rau vector tom, raws li qhia rau Aedes salivary gland protein extract [106] thiab An. gambiae D7s [107]. Lawv lub peev xwm los tawm tsam kev tiv thaiv kab mob kuj tseem ua rau lawv cov neeg sib tw tshuaj tiv thaiv zoo, xws li PdSP15, OBP-zoo li salivary protein uas pom tias yog tus neeg sib tw txhaj tshuaj tiv thaiv kab mob leishmaniasis [47].
Tus sau kev koom tes:
PHA thiab JFA tau tshuaj xyuas cov ntaub ntawv, sau thawj tsab ntawv ntawm cov ntawv sau, hloov kho cov ntawv sau tom ntej, thiab pom zoo rau cov ntawv kawg. Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.
Nyiaj txiag:
Txoj haujlwm no tau txais nyiaj los ntawm Intramural Research Program ntawm NIAID, National Institutes of Health.
Institutional Review Board Statement:
Tsis siv tau.
Cov Lus Qhia Txog Kev Pom Zoo:
Tsis siv tau.
Cov ntaub ntawv muaj nyob:
Tsis siv tau.
Kev lees paub:
Cov kws sau ntawv ua tsaug José Marcos Chaves Ribeiro rau kev tshuaj xyuas cov ntawv sau no thiab muab cov lus qhia muaj txiaj ntsig thiab cov lus pom.
Kev tsis sib haum xeeb ntawm kev txaus siab:
Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab.
Cov ntaub ntawv
1. Ribeiro, JM Lub luag haujlwm ntawm cov qaub ncaug hauv ntshav pub los ntawm arthropods. Annu. Rev. Entomol. Xyoo 1987, 32, 463–478. [CrossRef] [PubMed]
2. Ribeiro, JM; Francischetti, IM Lub luag haujlwm ntawm arthropod qaub ncaug hauv ntshav pub mis: Sialome thiab post-sialome foundations. Annu. Rev. Entomol. Xyoo 2003, 48, 73–88. [CrossRef] [PubMed]
3. Graca-Souza, AV; Maya-Monteiro, C.; Paiva-Silva, GO; Braz, GR; Paes, MC; Sorgine, MH; Oliveira, IB; Oliveira, PL Adaptations tiv thaiv heme toxicity nyob rau hauv cov ntshav pub arthropods. Kab Biochem. Mol. Biol. 2006, 36, 322–335. [CrossRef] [PubMed]
4. Ribeiro, JM Blood-feeding arthropods: Live syringes or invertebrate pharmacologists? Kab mob. Agents Dis. 1995, 4, 143–152. [PubMed]
5. Ribeiro, JM; Mas, BJ; Arca, B. Kev nkag siab rau hauv sialome ntawm ntshav pub Nematocera. Kab Biochem. Mol. Biol. Xyoo 2010, 40, 767–784. [CrossRef]
6. Ribeiro, JMC; Arcà, B. Tshooj 2 los ntawm Sialomes mus rau Sialoverse. Ua ntej hauv Kab Physiology; Elsevier: Amsterdam, Lub Netherlands, 2009; ib., 59–118.
7. Andersen, JF Structure thiab mechanism nyob rau hauv salivary proteins los ntawm cov ntshav arthropods. Toxicon 2010, 56, 1120–1129. [CrossRef]
8. Arca, B.; Ribeiro, JM Saliva ntawm cov kab hematophagous: Cov khoom siv ntau yam. Curr. Opin. Kab Sci. 2018, 29, 102–109. [CrossRef]
9. Cornwall, J.; Patton, W. Qee qhov kev soj ntsuam ntawm cov qaub ncaug ntawm cov kab mob ntshav nqus thiab cov zuam. Indian J. Med. Res. 1914, 2, 569–593.
10. Lester, H.; Lloyd, L. Notes on the Process of digestion in Tsetse-flies. Bull. Entomol. Res. 1928, 19, 39–60. [CrossRef]
11. Ribeiro, J.; Garcia, E. Lub luag haujlwm ntawm cov qog qaub ncaug hauv kev pub mis hauv Rhodnius prolixus. J. Exp. Biol. 1981, 94, 219–230. [CrossRef]
12. Ribeiro, JM; Rossignol, PA; Spielman, A. Lub luag haujlwm ntawm yoov tshaj cum hauv cov hlab ntsha. J. Exp. Biol. 1984, 108, 1–7. [CrossRef]
13. Ribeiro, J.; Rossignol, P. Spielman, A. Salivary gland apyrase txiav txim siab lub sij hawm soj ntsuam hauv yoov tshaj cum anopheline. J. Kab Physiol. 1985, 31, 689–692. [CrossRef]
14. Valenzuela, JG High-throughput le caag los kawm salivary proteins thiab noob los ntawm vectors ntawm tus kab mob. Kab Biochem. Mol. Biol. 2002, 32, 1199–1209. [CrossRef] 15. Mans, B.; Francischetti, I. Sialomic foundations ntawm evolution ntawm kev noj ntshav coj cwj pwm nyob rau hauv Arthropods: yav tom ntej kho los ntawm ntuj tsim. Hauv cov tshuaj lom thiab hemostasis; Springer: Dordrecht, Lub Netherlands, 2010; ib., 21–44.
16. Txiv neej, BJ Evolution ntawm vertebrate hemostatic thiab inflammatory tswj mechanisms nyob rau hauv cov ntshav pub arthropods. J. Innate Immun. 2011, 3, 41–51. [CrossRef] [PubMed] 17. Valenzuela, JG; Charlab, R.; Gonzalez, EC; de Miranda-Santos, IK; Marinotti, UA; Francischetti, IM; Ribeiro, JM Tsev neeg D7 ntawm salivary proteins nyob rau hauv cov ntshav nqus Diptera. Kab Mol. Biol. 2002, 11, 149–155. [CrossRef] [PubMed]
18. Calvo, E.; de Bianchi, AG; James, UA; Marinotti, O. Cov kua qaub-soluble proteins loj ntawm cov poj niam laus Anopheles darlingi salivary qog muaj xws li ib tug tswv cuab ntawm D7-txog tsev neeg cov proteins. Kab Biochem. Mol. Biol. 2002, 32, 1419–1427. [CrossRef]
