Protein X of Hepatitis B Virus Origin and Structure Similarity with the Central Domain of DNA Glycosylase 英文参考文献.docVIP

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Protein X of Hepatitis B Virus Origin and Structure Similarity with the Central Domain of DNA Glycosylase 英文参考文献.doc

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Protein X of Hepatitis B Virus Origin and Structure Similarity with the Central Domain of DNA Glycosylase 英文参考文献

ProteinXofHepatitisBVirus:OriginandStructure SimilaritywiththeCentralDomainofDNAGlycosylase FormijnJ.vanHemert1*,MaartenA.A.vandeKlundert3,VladimirV.Lukashov1*,NeeltjeA.Kootstra3, BenBerkhout1,HansL.Zaaijer2,3 1Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 2Laboratory Clinical Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 3Laboratory of Experimental Immunology, Department of MedicalMicrobiology,CenterforInfectionandImmunityAmsterdam(CINIMA),AcademicMedicalCenter,UniversityofAmsterdam,Amsterdam,TheNetherlands Abstract Orthohepadnavirus(mammalianhosts)andavihepadnavirus(avianhosts)constitutethefamilyofHepadnaviridaeanddiffer by their capability and inability for expression of protein X, respectively. Origin and functions of X are unclear. The evolutionaryanalysisatissueofXindicatesthatpresentstrainsoforthohepadnavirusstartedtodivergeabout25,000years ago,simultaneouslywiththeonsetofavihepadnavirusdiversification.Theseevolutionaryeventswereprecededbyamuch longerperiodduringwhichorthohepadnavirusdevelopedafunctionalproteinXwhileavihepadnavirusevolvedwithoutX. Aninsilicogenerated3D-modeloforthohepadnaviralXproteindisplayedconsiderablesimilaritytothetertiarystructureof DNAglycosylases(keyenzymesofbaseexcisionDNArepairpathways).SimilarityisconfinedtothecentraldomainofMUG proteins with the typical DNA-binding facilities but without the capability of DNA glycosylase enzymatic activity. The hypotheticaltranslationproductofavestigialXreadingframeinthegenomeofduckhepadnaviruscouldalsobeenfolded intoaDNAglycosylase-like3D-structure.Inconclusion,themostrecentcommonancestorofortho-andavihepadnavirus carriedanXsequencewithorthologytothecentraldomainofDNAglycosylase. Citation:vanHemertFJ,vandeKlu