簡介
邵峰,男,博士,北京生命科學研究所資深研究員,中國生物化學與分子生物學會蛋白質專業委員會委員。
研究興趣集中在病原細菌感染宿主和宿主先天性免疫防禦的分子機制。對於細菌感染來說,通過特殊的分泌系統向宿主細胞中注入毒素效應蛋白是病原細菌普遍採用的重要致病機制。這些效應蛋白往往以非常有效的方式作用於宿主信號轉導中的關鍵分子,使其發生功能紊亂。效應蛋白的作用有利於細菌在宿主中的生存和進一步感染。他率領的團隊研究以多種臨床上常見的病原菌(Shigella,Salmonella,EnteropathogenicE.coli,Legionella以及Burkholderia)為模式,著眼於發現並揭示效應蛋白在抑制真核細胞重要信號轉導通路中的一些新的、較為普遍的生物化學機制。最近的研究工作在這方面取得了一系列的突破和發現。1)來源於Shigella,Salmonella和植物假單胞桿菌的OspF家族三型分泌系統效應蛋白通過一種嶄新的磷酸化蘇氨酸裂合酶的活性,特異性地、不可逆地“去磷酸化”宿主MAPK激酶並使其失活,從而抑制宿主細胞因子的表達。2)Legionella的四型分泌系統效應蛋白LegK1能模擬宿主中的IKK激酶而磷酸化IκBa蛋白,並誘導其被泛素化和降解,進而激活NF-κB通路並對巨噬細胞凋亡產生抑制作用。3)三型分泌系統效應蛋白CHBP(Burkholderia)和Cif(EnteropathogenicE.coli)特異性地修飾(脫氨)泛素和泛素樣蛋白NEDD8中GLN-40。這種修飾能有效地阻斷宿主泛素-蛋白酶體通路並導致諸如細胞周期等重要細胞生理過程發生功能紊亂。研究團隊認為,這些研究不僅對理解感染和致病的分子機理有極大的促進作用,更為重要的是,由於病原細菌和宿主(人類)長期共同進化,其分泌的毒素效應蛋白也為我們研究真核細胞本身的信號轉導機制提供了獨特的、前所未有的視角和研究工具。同時,研究團隊也對宿主巨噬細胞如何通過其先天性免疫系統來拮抗病原微生物感染的機制感興趣。在受到感染後,巨噬細胞能感受到多種來自病原菌或其它病原微生物的一些模式分子,從而激活一類被稱為炎症小體的蛋白複合物,同時發生炎症性細胞壞死和分泌白介素1b。炎症小體利用一類叫作NOD-like的受體分子感受來自病原菌的信號,但除此之外人們對炎症小體的組裝和其上游的信號轉導機制了解甚少。研究團隊將結合生物化學、細胞生物學以及小鼠遺傳學等多種手段來研究和闡明炎症小體被激活的生化機制。
獲國際蛋白質學會青年科學家獎
因在病原菌和宿主相互作用分子機制研究方面取得一系列原創性成果,邵峰博士2013年2月獲得了國際蛋白質學會頒發的青年科學家獎,是首位獲得此項殊榮的中國本土科學家。
邵峰通過研究致病細菌如何通過調節宿主細胞的多層信號通路而逃避其免疫反應的機理,獲得了幾個關鍵的科學發現。比如,發現了導致RhoGTP酶從宿主細胞膜上脫離的一個半胱氨酸蛋白水解酶家族,以及幾個影響泛素信號轉導的細菌因子等。基於這些重要科學發現,國際蛋白質學會決定將2013年的青年科學家獎授予邵峰。
論文
Researcharticles:
1.DongN,ZhuY,LuQ,HuL,ZhengY,shaoF.(2012)StructurallyDistinctBacterialTBC-likeGAPsLinkArfGTPasetoRab1InactivationtoCounteractHostDefenses.Cell,150,1029-41.
2.GeJ,GongYN,XuY,ShaoF.(2012)PreventingbacterialDNAreleaseandabsentinmelanoma2inflammasomeactivationbyaLegionellaeffectorfunctioninginmembranetrafficking.Proc.Natl.Acad.Sci.,109,6193-8.
3.ZhangL,DingX,CuiJ,XuH,ChenJ,GongYN,HuL,ZhouY,GeJ,LuQ,LiuL,ChenS,ShaoF.(2012)Cysteinemethylationdisruptsubiquitin-chainsensinginNF-kBactivation.Nature,481,204-8.
4.ZhaoY,YangJ,ShiJ,GongYN,LuQ,XuH,LiuL,ShaoF.(2011)TheNLRC4inflammasomereceptorsforbacterialflagellinandtypeIIIsecretionapparatus.Nature,477,596–600.
5.CuiJ,YaoQ,LiS,DingX,LuQ,MaoH,LiuL,ZhengN,ChenS,ShaoF.(2010)Glutaminedeamidationanddysfunctionofubiquitin/NEDD8inducedbyabacterialeffectorfamily.Science,329,1215-8.
6.GongYN,WangX,WangJ,YangZ,LiS,YangJ,LiuL,LeiX,ShaoF.(2010)Chemicalprobingrevealsinsightsintothesignalingmechanismofinflammasomeactivation.CellResearch,20,1289-305.
7.DongN,LiuL,ShaoF.(2010)AbacterialeffectortargetshostDH-PHdomainRhoGEFsandantagonizesmacrophagephagocytosis.EMBOJ.,29,1363-76.
8.ZhuY,HuL,ZhouY,YaoQ,LiuL,ShaoF.(2010)StructuralmechanismofhostRab1activationbythebifunctionalLegionellatypeIVeffectorSidM/DrrA.Proc.Natl.Acad.Sci.,107,4699-704.
9.GeJ,XuH,LiT,ZhouY,ZhangZ,LiS,LiuL,ShaoF.(2009)ALegionellatypeIVeffectoractivatestheNF-κBpathwaybyphosphorylatingtheIκBfamilyofinhibitors.Proc.Natl.Acad.Sci.,106,13725-30.
10.ChenY,YangZ,MengM,ZhaoY,DongN,YanH,LiuL,DingM,Peng,HB,ShaoF.(2009)CullinmediatesdegradationofRhoAthroughevolutionarilyconservedBTBadaptorstocontrolactincytoskeletonstructureandcellmovement.Mol.Cell,35,841-55.
11.YaoQ,CuiJ,ZhuY,WangG,HuL,LongC,Cao,R,LiuX,HuangN,ChenS,LiuL,ShaoF.(2009)AbacterialtypeIIIeffectorfamilyusesthepapain-likehydrolyticactivitytoarrestthehostcellcycle.Proc.Natl.Acad.Sci.,106,3716-21.
12.ZhuY.,LiH.,HuL.,Wang,J.,ZhouY.,PangZ.,LiuL.,ShaoF.(2008)StructureofaShigellaeffectorrevealsanewclassofubiquitinligases.NatureStructural&MolecularBiology,15,1302-8.
13.ZhuY,LiH,LongC,HuL,XuH,LiuL,ChenS,WangDC,ShaoF.(2007)StructuralinsightsintotheenzymaticmechanismofthepathogenicMAPKphosphothreoninelyase.Mol.Cell,28,899-913.
14.ZhangJ,ShaoF,LiY,CuiH,ChenL,LiH,ZouY,LongC,LanL,ChaiJ,ChenS,TangX,ZhouJM.(2007)APseudomonassyringaeeffectorinactivatesMAPKstosuppressPAMP-inducedimmunity.CellHostµbe,1,175-85.
15.LiH,XuH,ZhouY,ZhangJ,LongC,LiS,ChenS,ZhouJM,ShaoF.(2007)ThephosphothreoninelyaseactivityofabacterialtypeIIIeffectorfamily.Science,315,1000-3.
16.AltoNM,ShaoF,LazarCS,BrostRL,ChuaG,Mattoo,SM,McMahonSA,GhoshP,HughesTR,BooneC,DixonJE.(2006)IdentificationofabacterialtypeIIIeffectorfamilywithG-proteinmimicryfunctions.Cell,124,133-45.
17.ZhuM,ShaoF,InnesRW,DixonJE,XuZ.(2004)ThecrystalstructureofPseudomonasavirulenceproteinAvrPphB:apapain-likefoldwithadistinctsubstrate-bindingsite.Proc.Natl.Acad.Sci.,101,302-7.
18.ShaoF,Golstein,C,AdeJ,StoutemyerM.,DixonJE,InnesRW.(2003)CleavageofArabidopsisPBS1byabacterialtypeIIIeffector.Science,301,1230-3.
19.ShaoF,VacratsisPO,BaoZ,BowersKE,FierkeCA,DixonJE.(2003)BiochemicalcharacterizationoftheYersiniaYopTprotease:cleavagesiteandrecognitionelementsinRhoGTPases.Proc.Natl.Acad.Sci.,100,904-9.
20.ShaoF,MerrittPM,BaoZ,InnesRW,DixonJE.(2002)AYersiniaeffectorandaPseudomonasavirulenceproteindefineafamilyofcysteineproteasesfunctioninginbacterialpathogenesis.Cell,109,575-88.
21.ShaoF,BaderMW,JakobU,BardwellJC.(2000)DsbG,aproteindisulfideisomerasewithchaperoneactivity.J.Biol.Chem.,275,13349-52.
22.ShaoF,HuZ,XiongYM,HuangQZ,WangCG,ZhuRH,WangDC.(1999)AnewantifungalpeptidefromtheseedsofPhytolaccaamericana:characterization,aminoacidsequenceandcDNAcloning.Biochim.Biophys.Acta,1430,262-8.
23.ShaoF,XiongYM,ZhuRH,LingM,ChiCW,WangDC.(1999)ExpressionandpurificationoftheBmKM1neurotoxinfromthescorpionButhusmartensiiKarsch.ProteinExpr.Purif.,17,358-65.
Invitedreviewarticles:
24.ZhaoY,ShaoF.(2012)NLRC5:aNOD-likereceptorproteinwithmanyfacesinimmuneregulation.CellResearch,22,1099-101.
25.GongYN,ShaoF.(2012)SensingbacterialinfectionsbyNAIPreceptorsinNLRC4inflammasomeactivation.Protein&Cell,3,98-105.
26.GeJ,ShaoF.(2011)ManipulationofhostvesiculartraffickingandinnateimmunedefensebyLegionellaDot/Icmeffectors.Cell.Microbiol.,13,1870-80.
27.CuiJ,ShaoF.(2011)Biochemistryandcellsignalingtaughtbybacterialeffectors.TrendsinBiochemicalSciences,36,532-40.
28.ShaoF.(2008)BiochemicalfunctionsofYersiniatypeIIIeffectors.CurrentOpinioninMicrobiology,11,21-9.
29.JurisSJ,ShaoF,DixonJE.(2002)Yersiniaeffectorstargetmammaliansignalingpathways.Cell.Microbiol.,4:201-11(Co-firstauthor).