Ib qho kev piav qhia ntawm D7 Protein Structure Thiab Physiological Roles nyob rau hauv cov ntshav pub Nematocera Part 1
Jun 14, 2023
Cov ntsiab lus yooj yim:
Vectors yog cov kab mob uas kis tau cov kab mob kis los ntawm ib tus tswv tsev (tib neeg lossis tsiaj) mus rau lwm tus. Ntau tus kab mob (xws li yoov tshaj cum, xuab zeb yoov, thiab zuam) muaj ib qho zoo sib xws: lawv yog cov ntshav pub ntshav (hematophagous) arthropods. Txhua zaus lawv tom lawv tus tswv tsev vertebrate, daim tawv nqaij thiab vascular raug mob ua rau muaj ntau cov lus teb uas nyob rau hauv qhov chaw tuaj yeem ua rau muaj kev cuam tshuam ntawm cov ntshav ntws mus rau lawv lub qhov ncauj, thiab ua kom muaj kev paub txog vim khaus thiab mob. Txawm li cas los xij, lawv cov qaub ncaug muaj cov dej cawv ntawm cov molecules uas muaj peev xwm tiv thaiv cov lus teb ntawm tus tswv tsev (hemostasis, o, thiab tiv thaiv kab mob), tso cai rau lawv noj kom zoo.
Ntau zaus, cov kab mob uas lawv kis tau raug txhaj rau hauv tus tswv tsev nrog qaub ncaug. Yog li ntawd, kev nkag siab txog cov kab mob ntawm cov qaub ncaug yog qhov tseem ceeb rau kev kawm txog lawv cov biology, thiab lawv lub peev xwm vectorial, nrog rau kev tawm tswv yim tshiab los tswj cov kab mob uas lawv kis tau (xws li cov neeg sib tw tshuaj tiv thaiv tshiab). Ntawm cov tsev neeg salivary protein tseem ceeb yog D7, nthuav qhia ntau hauv cov ntshav nqus Diptera thiab nyob deb ntawm Odorant-Binding Proteins (OBP). Ntawm no, peb muab kev tshuaj xyuas dav dav ntawm D7 protein cov qauv, kev ua haujlwm, thiab kev hloov pauv, sib tham txog yuav ua li cas cov noob duplication thiab kev hloov kho hauv lawv cov OBP-zoo li domains ua rau qhov nce thiab poob ntawm kev ua haujlwm hauv ntau hom hematophagous Diptera.
Cov kab mob sib kis tuaj yeem ua rau muaj kab mob, thiab lub cev tiv thaiv kab mob yog lub luag haujlwm tiv thaiv cov kab mob no thiab tiv thaiv kev kis kab mob. Lub cev tiv thaiv kab mob ua lub luag haujlwm tseem ceeb hauv kev txheeb xyuas thiab rhuav tshem cov kab mob. Cov kab mob kis tau ua rau lub cev tsis muaj zog los tsim cov tshuaj tiv thaiv kab mob thiab cov tshuaj tiv thaiv kab mob hauv lub cev uas tiv thaiv kev rov ua dua tshiab.
Txawm li cas los xij, qee yam kab mob tuaj yeem hla lossis ua rau lub cev tsis muaj zog tiv thaiv cov txheej txheem tiv thaiv, ua rau txo qis kev tiv thaiv thiab yog li ua rau muaj kev pheej hmoo kis mob. Piv txwv li, HIV tuaj yeem tawm tsam lub cev tsis muaj zog CD4 ntxiv rau T hlwb, cuam tshuam lub cev tsis muaj zog thiab ua kom kis tau yooj yim dua.
Tsis tas li ntawd, kev tiv thaiv tsis muaj zog tuaj yeem ua rau qee yam kab mob hnyav dua thiab nyuaj kho. Yog li ntawd, kev nkag siab txog kev sib raug zoo ntawm cov kab mob sib kis thiab kev tiv thaiv kab mob yog qhov tseem ceeb heev rau kev tiv thaiv thiab kho cov kab mob sib kis. Los ntawm qhov kev xav no, peb yuav tsum txhim kho kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv zoo. Cov polysaccharides hauv cov nqaij tuaj yeem tswj hwm kev tiv thaiv kab mob ntawm tib neeg lub cev tiv thaiv kab mob, txhim kho kev ntxhov siab ntawm lub cev tiv thaiv kab mob, thiab txhim kho cov kab mob bactericidal ntawm lub cev tiv thaiv kab mob.
Abstract:
Txhua lub sij hawm tus kab tom ib tus tswv tsev vertebrate, daim tawv nqaij thiab vascular raug mob los ntawm kev tho ua rau muaj ntau cov lus teb xws li hemostasis, o, thiab tiv thaiv kab mob. Nyob rau hauv qhov chaw, cov txheej txheem ntawm cov lus teb tsis sib xws thiab sib cuam tshuam yuav kawg ua rau cov ntshav coagulation, khaus, thiab mob ua rau muaj kev paub txog tus tswv, ua rau muaj kev cuam tshuam rau kev noj zaub mov zoo tshaj plaws. Txawm li cas los xij, hematophagous arthropod qaub ncaug muaj cov kab mob sib xyaw ua ke ntawm cov molecules uas tseem ceeb heev rau kev ua tiav ntawm kev noj ntshav.
Ntawm cov tsev neeg protein tseem ceeb tau piav qhia txog tam sim no nyob rau hauv cov qaub ncaug ntawm cov ntshav nqus cov arthropods, yog D7, abundantly qhia nyob rau hauv cov ntshav pub Nematocera. D7 cov proteins nyob deb ntawm cov kab Odorant-Binding Proteins (OBP), thiab txawm tias tsis tshua muaj cov cim qhia txog tus kheej, kev soj ntsuam ntawm cov qauv zoo sib xws tau coj mus rau cov lus pom zoo uas zoo li OBPs, lawv yuav tsum khi/sequester me me hydrophobic compounds. Cov tswv cuab ntawm tsev neeg no tau muab faib ua cov ntawv luv thiab cov ntawv ntev, muaj ib lossis ob lub OBP-zoo li tus thawj, raws li. Ntawm no, peb muab kev tshuaj xyuas ntawm D7 protein cov qauv thiab kev ua haujlwm, sib tham txog yuav ua li cas gene duplication thiab qee qhov kev hloov kho hauv lawv cov OBP-zoo li domains thaum lub sij hawm evolution ua rau nce thiab poob ntawm kev ua haujlwm ntawm ntau hom hematophagous Diptera.
Ntsiab lus:
D7 proteins; odorant-binding proteins; vector biology; hematophagy; vector kua qaub; hemostasis; mob.
1. Taw qhia
Cov kab mob uas kis los ntawm cov kab mob muaj ntau haiv neeg ntawm cov tsos mob, yam ntxwv, cov kab mob etiologic, thiab lawv cov vectors. Txawm hais tias muaj ntau haiv neeg no, ib qho kev sib koom ua ke los ntawm cov vectors paub ntau yog qhov tseeb tias lawv yog hematophagous arthropods. Kev muaj peev xwm noj ntshav ua rau muaj teeb meem ntau yam nrog rau lub peev xwm los nrhiav tus tswv tsev, tho nws cov tawv nqaij thiab nrhiav cov ntshav, nqus cov ntshav kom tom qab zom nws, thiab cuam tshuam nrog oxidative kev nyuaj siab los ntawm nws txoj hnyuv (saib hauv [1–3] ).
Txhua lub sij hawm tus kab tom nws tus tswv tsev vertebrate, daim tawv nqaij thiab vascular raug mob ua rau muaj cov lus teb xws li hemostasis, o, thiab tiv thaiv kab mob [1,2,4–8]. Cov txheej txheem lom neeg tsis txaus ntseeg no muaj kev sib cuam tshuam thiab muaj peev xwm nthuav tawm vim yog kev tsim khoom / tso tawm ntawm ntau cov chav kawm ntawm cov neeg kho kom haum xeeb, suav nrog eicosanoids, biogenic amines, coagulation, thiab ntxiv yam.
Nyob rau hauv qhov chaw, lawv yuav ua rau muaj kev cuam tshuam ntawm cov ntshav ntws mus rau lub qhov ncauj ntawm lub hematophagous arthropod (vim yog vascular constriction, platelet aggregation, thiab ntshav coagulation) thiab ua rau tus tswv tsev paub (vim khaus thiab mob). Txawm li cas los xij, cov qaub ncaug ntawm cov ntshav pub rau arthropods muaj qhov sib npaug sib npaug thiab sib xyaw ua ke ntawm cov molecules muaj peev xwm tiv thaiv tus tswv tsev tiv thaiv ua lub luag haujlwm tseem ceeb hauv kev ua tiav ntawm hematophagy (saib hauv [1,2,4-8]). Tseeb, raws li tau hais ua ntej los ntawm Ribeiro, hematophagous arthropods yog "nyob syringes" thiab lawv cov qaub ncaug tseem yog ib qho tseem ceeb ntawm cov tshuaj pharmacologically active molecules [4].
Lub xub ntiag ntawm anticoagulant molecules nyob rau hauv hematophagous arthropods ' qaub ncaug yog thawj zaug tshaj tawm nyob rau hauv thaum pib ntawm lub xyoo pua xeem [9,10], thiab ua qauv qhia txog qhov tseem ceeb ntawm salivary secretion nyob rau hauv cov ntshav pub thawj zaug nyob rau hauv lub 800s [11-13] . Txawm li cas los xij, muaj pes tsawg leeg ntawm cov qaub ncaug thiab cov haujlwm tshwj xeeb ntawm nws cov khoom tseem tsis tau nkag siab. Kev siv cov txheej txheem loj thiab cov proteomics ntau xyoo dhau los tso cai rau kev nkag siab zoo ntawm cov qaub ncaug muaj pes tsawg leeg tab sis kuj qhia nws qhov nyuaj thiab paub tsawg npaum li cas [2,14]. Vim hais tias hematophagy tau tshwm sim ntawm nws tus kheej ob peb zaug thaum lub sij hawm arthropod evolution, ntau txoj hauv kev los daws cov teeb meem los ntawm tus cwj pwm no tshwm sim ntawm cov kab sib txawv, lossis txawm nyob rau hauv tib lub genus ua rau muaj kev sib txawv ntawm cov repertoire ntawm cov protein los tiv thaiv tus tswv tsev tiv thaiv. [2, 4, 5, 7, 15, 16].
Ntawm cov tsev neeg protein tseem ceeb tau piav qhia txog tam sim no nyob rau hauv cov qaub ncaug ntawm cov ntshav nqus cov arthropods, yog D7, abundantly qhia nyob rau hauv hematophagous Diptera [17-19] thiab deb ntawm kab ntsig txog kab Odorant-Binding Proteins (OBP) / Pheromone-Binding Proteins (PBP) .
Hauv kab, OBPs feem ntau muaj li ntawm 100 txog 160 residues, tab sis raws li tau pom rau qee cov tswv cuab ntawm "atypical/ob domains" lossis "Plus C" sub-tsev neeg tau piav qhia hauv Diptera, uas tuaj yeem muaj txog 300 amino acids [20–22. ]. Lawv tam sim no nyob rau hauv ntau yam kev txiav txim thiab tus naj npawb ntawm annotated OBP noob sib txawv ntau ntawm ntau hom, nrog rau cov amino acid sequence.
Txawm li cas los xij, lawv cov cysteines tau txais txiaj ntsig zoo - classic 6, txawm hais tias tus lej no tuaj yeem sib txawv ntawm 4 hauv rho tawm C OBPs mus rau 8 ntxiv rau OBPs rau txawm tias 9 lossis 10 - nyob rau hauv cov saw hlau polypeptide nrog kos npe nyob deb ntawm qee qhov [20,21. , 23] ib. Sib txawv ntawm OBPs vertebrates, uas yog tag nrho cov proteins uas yog cov lipocalins superfamily (SCOP: 3001332), kab OBPs raug cais raws li tag nrho cov proteins thiab belongs rau kab pheromone / odorant-binding superfamily (SCOP ID: 4000957). Txawm hais tias tsis tshua muaj tus kheej sib txawv ntawm cov tswv cuab, cov kab mob classical OBPs muaj cov qauv zoo heev, nrog rau 6 -cov helices feem ntau ruaj khov los ntawm 3 disulfide daim ntawv cog lus tsim cov kab noj hniav (Daim duab 1A), nyob ib puag ncig los ntawm hydrophobic residues [20,24-26. ]. Tus lej loj thiab ntau haiv neeg ntawm lawv cov qauv tseem ceeb, thaum tswj xyuas tag nrho cov qauv tsim, ua rau lawv muaj ntau yam ntawm ligands, tab sis tag nrho nrog ib tus yam ntxwv sib xws: lawv lub peev xwm / peev xwm los khi me me hydrophobic molecules.
D7 proteins, txawm li cas los xij, raug txwv rau kev pub ntshav Nematocera, uas lawv tau nthuav tawm ntau hauv lawv cov qog qaub ncaug. Cov tswv cuab ntawm tsev neeg no tau muab faib ua (1) cov ntawv luv luv (D7S), tseem hu ua D7 ntsig txog (D7r), nrog qhov hnyav molecular nyob ib ncig ntawm 15–17 kDa, muaj ib qho OBP-zoo li tus sau (Daim duab 1B); (2) cov ntawv ntev (D7L), nrog qhov hnyav molecular nyob ib ncig ntawm 30–38 kDa, tsim los ntawm ob lub OBP zoo li domains (Daim duab 1C). Raws li thawj zaug tau thov los ntawm Arcà thiab cov npoj yaig [27] thiab tom qab ntawd pom los ntawm X-ray diffraction crystallography [7,28-30], txawm tias lawv qhov qis qis zoo sib xws rau OBPs, D7 protein domains architecture zoo ib yam li OBPs, tau tsim los ntawm - helices (feem ntau 7–8 -helices tab sis tsis yog 6), tsim ib lub hnab ntim hydrophobic (Daim duab 1B, C) haum rau khi hydrophobic molecules, raws li yuav tau tham ntxiv hauv qab no.
Feem ntau ntawm D7 cov proteins uas muaj nyob rau tam sim no tau pom nyob rau hauv cov qaub ncaug ntawm cov ntshav nqus Diptera, qhov chaw uas lawv ua raws li cov tshuaj tiv thaiv hemostatic thiab / lossis cov tshuaj tiv thaiv kab mob, pab txhawb kev noj ntshav. Hauv daim ntawv tam sim no, peb muab kev tshuaj xyuas dav dav ntawm D7 thiab D7-zoo li cov qauv protein, kev ua haujlwm, thiab kev hloov pauv, piv qee yam ntawm arthropod OBPs thiab lwm tsev neeg cov protein uas cuam tshuam rau vector physiology.
2. D7s: Los ntawm cov lus piav qhia ntawm Thawj Gene rau cov lus qhia txog lawv qhov kev sib txawv, kev faib tawm, thiab kev ua haujlwm
Thawj cov noob encoding ib D7 protein yog cais thiab piav nyob rau hauv 1991 nyob rau hauv Aedes aegypti [31], qhia tau hais tias muaj ntau thiab tshwj xeeb tshaj yog hais nyob rau hauv cov poj niam salivary qog ua ib tug 37 kDa protein. Nyob rau hauv situ hybridization siv dissected poj niam salivary qog soj ntsuam nrog antisense RNA rau lub coding cheeb tsam ntawm no gene qhia nws qhia tau tsuas yog nyob rau hauv lub distal lateral thiab medial lobes, cov cheeb tsam uas zoo heev txawv nyob rau hauv cov poj niam (hematophagous) thaum piv rau txiv neej (phytophagous) , qhia tias nws cov khoom muaj feem cuam tshuam rau kev noj ntshav. Tom qab ntawd, hauv kev tshawb nrhiav pioneering txhawm rau txheeb xyuas cov noob uas tau nthuav tawm tshwj xeeb hauv cov qog ua kua qaub ntawm Anopheles gambiae thiab nws cov khoom muaj cov teeb liab peptides, rau cDNA raug cais tawm.
Peb ntawm lawv, qhia tau hais tias muaj ntau ntau hauv cov qog ntshav poj niam, cov ntawv sau zoo sib xws, txawm tias luv dua, rau yav dhau los tau piav qhia Aedes aegypti D7, qhia tias qhov no yog tsev neeg protein tshiab. Tag nrho peb qhov sib xyaw ua ke tag nrho nrog Aedes D7 C-terminal domain, yog li hu ua D7-txog cov proteins (D7r): D7r1–D7r3 [32]. Ib yam li ntawd, lawv tau hais nyob rau hauv poj niam qhov chaw lateral lobes, txawm hais tias tsuas yog ib qho ntawm lawv (D7r1) tau hais nyob rau hauv nruab nrab lobes ib yam nkaus [32].
Ob peb xyoos tom qab ntawd, plaub D7r (D7r4) kuj tau pom nyob rau hauv Anopheles gambiae poj niam qaub ncaug qog thiab pom tias nyob ze rau lwm yam peb daim ntawv ua ib pawg ntawm chromosome 3R [27]. Thaum ua tiav, 4 cov ntawv sau tseg no muaj qhov sib xws ntawm lawv li ntawm 53 txog 73 feem pua , thiab qhov tseem ceeb heev, lawv muaj qib qis ntawm qhov zoo sib xws rau OBPs thiab Pheromone binding Proteins (PBP), tab sis lawv 4 cysteine tau nyob ntawm kev txuag txoj haujlwm ntsig txog antennae. thiab tsis-antennal OBPs. Txawm hais tias tsis tshua muaj qhov sib xws, cov qauv kev twv ua ntej tau hais txog cov qauv zoo sib xws rau OBPs, yog li nws tau tshaj tawm tias D7s kuj tseem tuaj yeem muaj lub hnab ntim hydrophobic binding nyob ib puag ncig los ntawm -helices thiab muaj peev xwm los khi lossis nqa me me hydrophobic molecules, tej zaum cov neeg tuaj koom koom nrog cov tswv teb cov lus teb (xws li o thiab hemostasis), muab qhov tseeb tias lawv muaj ntau thiab tshwj xeeb rau poj niam qaub ncaug [27].
Qhov tseeb tias cov no An. gambiae luv cov ntaub ntawv raws li C-terminal ntawm Ae. aegypti D7L, thiab hais tias yav qab teb blot kev soj ntsuam pom lwm cov tswv cuab hauv cov tsiaj sib raug zoo tau tsa cov tswv cuab ntawm tsev neeg cov noob no tuaj yeem muaj nyob hauv lwm hom yoov tshaj cum thiab cov proteins uas muaj qhov ntev sib txawv ntawm cov noob no tuaj yeem muaj cov haujlwm zoo sib xws, tab sis cov hom phiaj sib txawv vim Yuav ua li cas los tsim lawv tus kheej [27]
Tseeb tiag, Suwan thiab cov neeg ua haujlwm tau tshaj tawm thawj zaug cov noob encoding ib D7L thiab 2 D7-cov ntaub ntawv ntsig txog (luv luv) hauv cov qog qaub ncaug ntawm Anopheles stephensi, thiab Western blot nrog polyclonal antibody tsim los paub txog cov protein ntev ntev tau hla. reactivity kuj nrog D7rs [33]. Qhov no yog thawj daim ntawv tshaj tawm qhia tias cov ntawv ntev thiab luv luv tuaj yeem pom hauv tib hom. Tom qab ntawd, cov kev tshawb fawb tom ntej tau tshaj tawm tias muaj lwm cov tswv cuab ntawm tsev neeg no nyob rau hauv ntau hom yoov tshaj cum (tsev neeg Culicidae) xws li Anopheles arabiensis, Aedes aegypti, thiab Anopheles darlingi [17,18], nrog rau lwm yam hematophagous Diptera uas yog tsev neeg Psychodidae ( xuab zeb yoov) [17].
Tag nrho cov kev tshawb fawb no tau pom zoo tias: (1) D7 yog ib tsev neeg ntawm cov proteins uas tej zaum yuav kis tau rau hauv hematophagous Diptera, tshwj xeeb tshaj yog nyob rau hauv cov qog ua kua qaub, yog li lawv yuav muaj lub luag haujlwm tseem ceeb hauv kev pub ntshav; (2) D7 proteins sib txawv nyob rau hauv ntev thiab amino acid ib theem zuj zus muaj nyob rau hauv ntau hom thiab nyob rau hauv tib hom, tej zaum yog ib tug tshwm sim ntawm gene duplication generating ntau haiv neeg; (3) lawv lub hom phiaj yuav tsum yog me me hydrophobic molecules, xws li o thiab / lossis hemostasis mediators [27,33]. Txawm li cas los xij, lawv txoj haujlwm tseem tsis tau paub.
3. Salivary D7 Proteins yog Anti-Inflammatory thiab Anti-Hemostatic Molecules
D7 thiab lwm yam OBP-zoo li cov proteins uas muaj nyob rau hauv cov qaub ncaug ntawm cov ntshav nqus Nematocera tuaj yeem muaj qhov sib txawv hauv lawv cov qauv, ua rau kom nce thiab poob haujlwm txawm tias khaws qee qhov tseem ceeb thiab cov qauv siv dav dav, raws li tau pom hauv ntau OBPs. Table 1 piav qhia txog D7 thiab D7-zoo li cov proteins uas tau piav qhia txog tam sim no nyob rau hauv cov qaub ncaug ntawm ntau hom, thiab lawv cov ligands thiab muab lawv cov Protein Data Bank (PDB) tus lej nkag, qhov twg siv tau. Cov ncauj lus kom ntxaws thiab qhov cuam tshuam ntawm lub cev tau tham hauv qab no.
3.1. Hu rau Pathway Inhibitors
Thawj D7 kom muaj nws qhov kev ua haujlwm yog ib daim ntawv luv luv (D7r), hu ua Hamadarin [35], qhia hauv SG ntawm Anopheles stephensi poj niam. Nws qhov ze tshaj D7 yog qhia hauv An. gambiae yog D7r1. Hamadarin tau pom tias khi Factor XII (FXII) thiab High Molecular Weigh Kininogen (HMWK) yog li inhibiting kev sib cuag txoj kev ua kom thiab ua rau bradykinin ntau lawm, ua raws li cov tshuaj tiv thaiv kab mob. Txawm li cas los xij, nyob rau hauv ob qho tib si, kev sib cuam tshuam nrog FXII thiab HMWK, kawm los ntawm Surface Plasmon Resonance (SPR), tsuas yog tshwm sim nyob rau hauv lub xub ntiag ntawm Zn2 ntxiv thiab tsis cuam tshuam rau activated yam amidolytic kev ua si. Es tsis txhob, nws cov nyhuv inhibitory ntawm kev sib cuag txoj kev ua kom yog vim nws cuam tshuam nrog kev sib txuas lus ntawm FXII thiab kallikrein uas yuav tsum tshwm sim thaum lawv cuam tshuam nrog qhov chaw them nyiaj [35]. Ob peb xyoos tom qab ntawd, lwm txoj kev sib txuas lus ua rau inhibitor muaj nyob rau hauv cov qaub ncaug ntawm Anopheles stephensi (Anophensin) tau tshwm sim thiab pom tias muaj lub hom phiaj zoo sib xws rau Hamadarin tab sis koom nrog tsev neeg protein sib txawv [42].
Qhov tsim nyog, ntawm cov protein ntau tshaj plaws hauv cov qaub ncaug qaub ncaug [43–45], yog ib pawg ntawm cov proteins uas tseem koom nrog OBP superfamily, tsis pom muaj yoov tshaj cum, thiab txawv ntawm D7 proteins. Lawv thawj zaug tau txais kev saib xyuas tsis yog rau lawv qhov kev nplua nuj xwb tab sis vim lawv tau txheeb xyuas tias yog cov tshuaj tiv thaiv kab mob Leishmaniasis [46,47]. Tsuas yog ntau tshaj li kaum xyoo tom qab ob tug tswv cuab ntawm pab pawg no tau tshwm sim hauv cov qaub ncaug ntawm Phlebotomus duboscqi: PdSP15a thiab PdSP15b (P. duboscqi Salivary Protein 15 a thiab b, ntsig txog). Ob leeg zoo ib yam li ib leeg thiab inhibit kev sib cuag kev ua kom thiab bradykinin ntau lawm [41] tab sis los ntawm ib qho kev sib txawv ntawm qhov tau piav qhia rau Hamadarin [35]. PdSP15a thiab b tsis khi rau tej yam coagulation (zymogens los yog activated forms), kallikrein, los yog prekallikrein. Lawv qhov kev ua tab sis yog los ntawm kev khi tsis zoo ntawm cov khoom siv polymers xws li dextran sulfate (DS), polyphosphate (PP), thiab heparin, tiv thaiv lawv cov kev cuam tshuam nrog FXII, tsim nyog rau nws qhov pib-cleavage uas ua rau nws ua kom muaj zog, thiab kev nthuav tawm tom qab ntawm kev sib cuag kev ua kom dhau los ntawm Reciprocal activation ntawm FXII thiab plasma prekallikrein (PK), nrog rau kev ua kom FXI los ntawm thrombin thiab FXIIa. Qhov tseem ceeb thaum OBPs classical thiab D7s muaj lub hnab ntim hydrophobic qhov twg lawv cov me me hydrophobic ligand khi, cov ntaub ntawv qhia txog nws cov txheej txheem ntawm kev ua haujlwm yog los ntawm electrostatic kev cuam tshuam ntawm nws cov anionic nto thiab tsis zoo li ligands, es tsis yog ib qho kev khi rau hauv cov kab noj hniav hydrophobic [41,47] .
Lub plasma coagulation cascade tuaj yeem pib los ntawm ob ceg sib txawv: (1) txoj hauv kev extrinsic, pib thaum qhov xwm txheej VII (FVII) tau qhib thaum khi rau cov ntaub so ntswg subendothelial (TF) tshwm sim tom qab vascular raug mob. (2) Txoj kev sib cuag, tseem hu ua txoj hauv kev, yog pib thaum ua kom FXII rau FXIIa tshwm sim los ntawm nws qhov kev sib cuag nrog qhov chaw tsis zoo. Ob txoj hauv kev tom qab muaj kev cuam tshuam ntau dhau mus rau txoj hauv kev los ntawm kev ua kom FX uas thaum kawg ua rau fibrinogen cleavage mus rau fibrin, qhov tseem ceeb rau kev tsim cov ntshav txhaws [48,49]. Nyob rau hauv xyoo tas los no, cov tshuaj tsom mus rau hauv txoj hauv kev (sib cuag) txoj hauv kev xws li FXII thiab FXI tau kawm ntau ntxiv txij li nws tau pom tias cov nas tsis muaj FXII raug tiv thaiv los ntawm kev tsim cov thrombus thaum tsis muaj qhov mob loj los ntshav [50–52], qhia txog txoj hauv kev no. Nws yog ib qho tseem ceeb rau kev loj hlob ntawm pathological coagulation.
Thaum ua kom tiav, yam XII cleaves plasma prekallikrein (PK) generating kallikrein, uas ntxiv rau reciprocal activation nrog FXII kuj catalyzes hydrolysis ntawm HMWK generating bradykinin (kallikrein-kinin system) [53]. Bradykinin yog ib tug muaj zog pro-inflammatory mediator uas nce endothelial permeability [48,54] thiab mob [55]. Yog li ntawd, muaj kev tiv thaiv kab mob hauv cov qaub ncaug ntawm hematophagous arthropods yuav ua lub luag haujlwm tseem ceeb hauv cov tshuaj tiv thaiv kab mob los ntawm kev txo qis bradykinin ntau lawm (raws li qhia rau D7s / OBP-zoo li cov proteins hamada hauv [35] thiab PdSP15s [41]). , thiab los ntawm inhibiting / tiv thaiv plasma leakage induced los ntawm kev sib cuag txoj kev ua kom raws li qhia rau PdSP15s [41].
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