Selective Ligand Recognition by a Diversity-Generating Retroelement Variable Protein 英文参考文献.docVIP

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Selective Ligand Recognition by a Diversity-Generating Retroelement Variable Protein 英文参考文献.doc

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Selective Ligand Recognition by a Diversity-Generating Retroelement Variable Protein 英文参考文献

o PL SBIOLOGY SelectiveLigandRecognitionbya Diversity-GeneratingRetroelement VariableProtein Jason L.Miller1¤a,Johanne LeCoq1,Asher Hodes2,3,Roman Barbalat2,3¤b,Jeff F.Miller2,3,Partho Ghosh1,4* 1DepartmentofChemistryandBiochemistry,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica,2DepartmentofMicrobiology,Immunology, andMolecularGenetics,DavidGeffenSchoolofMedicineatUCLA,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,3TheMolecular BiologyInstitute,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,4SectionofMolecularBiology,UniversityofCaliforniaSanDiego,La Jolla,California,UnitedStatesofAmerica Diversity-generating retroelements (DGRs) recognize novel ligands through massive protein sequence variation, a propertyshareduniquelywiththeadaptiveimmuneresponse.Littleisknownabouthowrecognitionisachievedby DGR variable proteins. Here, we present the structure of the Bordetella bacteriophage DGR variable protein major tropism determinant (Mtd) bound to the receptor pertactin, revealing remarkable adaptability in the static binding sites of Mtd. Despite large dissimilarities in ligand binding mode, principles underlying selective recognition were strikinglyconservedbetweenMtdandimmunoreceptors.Centraltothiswasthedifferentialamplificationofbinding strengthsbyavidity(i.e.,multivalency),whichnotonlyrelaxedthedemandforoptimalcomplementaritybetweenMtd and pertactin but also enhanced distinctions among binding events to provide selectivity. A quantitatively similar balance between complementarity and avidity was observed for Bordetella bacteriophage DGR as occurs in the immune system, suggesting that variable repertoires operate under a narrow set of conditions to recognize novel ligands. Citation:MillerJL,LeCoqJ,HodesA,BarbalatR,MillerJF,etal.(2008)Selectiveligandrecognitionbyadiversity-generatingretroelementvariableprotein.PLoSBiol6(6): e131.doi:10.1371/journal.pbio.0060131 (i.e., potential ph