UA RAWS
Cov txheej txheem tshiab tsim los ntawm pab pawg kws tshawb fawb ntawm Center for Genomic Regulation (CRG) hauv Barcelona tau tshawb pom qhov muaj ntau ntawm 'cov chaw taws teeb tswj' uas tswj cov haujlwm ntawm cov protein thiab tuaj yeem siv los ua lub hom phiaj kom ua tiav cov tshuaj zoo dua. thiab muaj txiaj ntsig zoo hauv ntau yam pathologies xws li dementia, mob qog noj ntshav thiab kis kab mob.
Cov 'cov chaw taws teeb tswj' no yog kev tshawb fawb hu ua allosteric sites. Cov no yog cov chaw taws teeb tswj uas nyob deb ntawm qhov chaw ua haujlwm ntawm cov protein, tab sis muaj peev xwm tswj hwm lossis hloov kho nws", Júlia Domingo, thawj tus kws sau ntawv ntawm kev tshawb fawb, uas tau tshaj tawm hnub Wednesday no hauv phau ntawv journal "Nature", piav qhia rau ABC. Thiab nws ntxiv ib qho piv txwv: "Nws zoo li yog tias nrog qhov chaw taws teeb tswj koj tuaj yeem tig lub teeb rau thiab tawm lossis tswj qhov siv ntawm lub teeb."
Nyob rau hauv rooj plaub no qhov twg nws npaj siab los thaiv lossis tswj cov haujlwm ntawm cov proteins uas tswj hwm lawv txoj haujlwm hloov pauv hauv kev kaw. Piv txwv li, nyob rau hauv cov ntaub ntawv ntawm kev mob qog noj ntshav, cov proteins uas tau txais kev hloov pauv tau hloov pauv lawv txoj haujlwm, lawv ua qhov txawv txav thiab lub cell loj hlob txawv txawv. Feem ntau, tsis muaj cov tshuaj uas tuaj yeem hloov kho lossis thaiv qhov kev ua haujlwm txawv txav no lossis, yog tias muaj, lawv tsis meej thiab tseem raug tso tawm los ntawm lwm cov proteins uas ua haujlwm ib txwm muaj.
Kev lig kev cai, cov neeg yos hav zoov tau tsim cov kev kho mob uas tsom mus rau qhov chaw nquag ntawm cov protein, uas nws cheeb tsam me tsim cov tshuaj tiv thaiv kab mob uas lub hom phiaj khi. Qhov tsis zoo ntawm cov tshuaj no, hu ua cov tshuaj orthosteric, yog qhov chaw ua haujlwm ntawm ntau cov proteins zoo sib xws thiab cov tshuaj tau khi thiab inhibited ntau yam proteins nyob rau tib lub sijhawm, txawm tias cov uas ua haujlwm ib txwm muaj thiab tsis nyiam kov, uas. tuaj yeem ua rau muaj kev phiv.
"Nws tau nkag mus rau lub tswv yim ntawm allosteria thiab lub peev xwm nws yuav tsum tau tsim tshuaj. Qhov nthuav txog qhov chaw allosteric yog tias lawv yog cov tshwj xeeb rau txhua cov protein. Yog tias cov chaw allosteric no pom ib feem ntawm cov protein nyob qhov twg cov tshuaj tuaj yeem tsaws, nws yuav yog qhov tshwj xeeb rau cov protein. Peb yuav muaj peev xwm xav tau cov tshuaj muaj txiaj ntsig zoo dua, ", taw qhia tus kws tshawb fawb.
"Tsis tsuas yog peb pom tias cov chaw kho mob no muaj ntau, tab sis muaj pov thawj tias lawv tuaj yeem siv tau ntau txoj hauv kev. Tsis yog tsuas yog tig rau thiab tawm, peb tuaj yeem hloov kho lawv cov haujlwm xws li ntsuas kub. Los ntawm qhov kev xav ntawm engineering, nws zoo li peb tau ntaus kub, vim nws muab ntau chav rau peb los tsim 'cov tshuaj ntse' uas mus rau qhov phem thiab hla qhov zoo", piav qhia André Faure, tus kws tshawb fawb tom qab kawm tiav ntawm CRG. thiab thawj co - tus sau ntawm tsab xov xwm.
Daim duab peb sab uas qhia txog tib neeg cov protein PSD95-PDZ3 los ntawm cov ntsiab lus sib txawv. Ib tug molecule yog qhia khi rau lub active site nyob rau hauv daj. Xiav rau xim liab xim gradient qhia tau tias muaj peev xwm allosteric qhov chaw - André Faure / ChimeraX
Rau qhov kev tshawb pom no, pab neeg no tau siv txoj hauv kev uas tso cai rau lawv coj cov protein thiab cov txheej txheem kev sib tham thiab kev sib ntsib thoob ntiaj teb nrog txhua qhov chaw. Ua li no, lawv tau xaiv ob qho protein ntau ntau hauv peb cov tib neeg proteome. "50% ntawm cov protein nto muaj peev xwm allosteric. Peb txoj kev ua rau nws muaj peev xwm ua kom muaj atlas ntawm qhov chaw allosteric, uas yuav ua rau cov txheej txheem ntawm kev tshawb nrhiav cov tshuaj muaj txiaj ntsig zoo dua ", lees paub Júlia Domingo.
Cov kws sau ntawv tshawb fawb tau tsim cov txheej txheem hu ua ob-depth PCA (ddPCA), uas lawv piav qhia tias yog "kev sim siab phem." "Peb lub hom phiaj rhuav tshem txhua yam hauv ntau txhiab txoj hauv kev los ua ib daim duab tiav ntawm qhov ua haujlwm li cas," piav qhia ICREA Research Professor Ben Lehner, Tus Thawj Saib Xyuas Haujlwm ntawm Systems Biology ntawm CRG thiab tus sau ntawm txoj kev tshawb no. "Nws zoo li yog tias koj xav tias lub tshuab hluav taws xob tsis zoo, tab sis tsis tsuas yog kuaj xyuas qhov ntawd, tus kws kho tsheb yuav muab tag nrho lub tsheb sib cais thiab xyuas tag nrho cov khoom ib zaug. Los ntawm kev tshuaj xyuas kaum txhiab yam ib zaug, peb txheeb xyuas tag nrho cov khoom uas tseem ceeb heev. "
Tom ntej no, peb siv cov cuab yeej txawj ntse algorithms los txhais cov txiaj ntsig ntawm kev kuaj.
Ib qho txiaj ntsig zoo ntawm txoj kev, ntxiv rau kev ua kom yooj yim cov txheej txheem tsim nyog los nrhiav cov chaw allosteric, yog tias nws yog cov txheej txheem pheej yig thiab siv tau rau txhua qhov chaw tshawb fawb hauv ntiaj teb. "Nws tsuas yog yuav tsum tau nkag mus rau cov txheej txheem molecular biology reagents, nkag mus rau DNA sequencer thiab lub computer. Nrog rau peb lub ntsiab lus no, ib qho chaw sim hauv 2-3 lub hlis, nrog rau kev siv nyiaj me me, tuaj yeem ua qhov kev sim no ntawm cov protein uas lawv xav tau, ", lees paub Júlia Domingo. Cov kws tshawb nrhiav kev cia siab yog tias peb cov kws tshawb fawb yuav siv cov txheej txheem kom sai thiab ua tiav daim duab qhia chaw allosteric ntawm tib neeg cov proteins ib los ntawm ib qho. "Yog tias peb muaj cov ntaub ntawv txaus tej zaum muaj ib hnub peb tuaj yeem mus ntxiv ib kauj ruam ntxiv thiab kwv yees los ntawm cov protein ntau ua haujlwm. Siv cov ntaub ntawv no los coj lawv li kev kho mob zoo dua los kwv yees yog tias muaj qee yam kev hloov pauv hauv cov protein yuav ua rau muaj kab mob, "tus kws tshawb fawb xaus lus.
