selective ligand recognition by a diversity-generating retroelement variable protein蛋白质选择性配体识别由diversity-generating retroelement变量.pdfVIP

PLoS BIOLOGY Selective Ligand Recognition by a Diversity-Generating Retroelement Variable Protein 1¤a 1 2,3 2,3¤b 2,3 1,4* Jason L. Miller , Johanne Le Coq , Asher Hodes , Roman Barbalat , Jeff F. Miller , Partho Ghosh 1 Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America, 2 Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America, 3 The Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America, 4 Section of Molecular Biology, University of California San Diego, La Jolla, California, United States of America Diversity-generating retroelements (DGRs) recognize novel ligands through massive protein sequence variation, a property shared uniquely with the adaptive immune response. Little is known about how recognition is achieved by 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 strikingly conserved between Mtd and immunoreceptors. Central to this was the differential amplification of binding strengths by avidity (i.e., multivalency), which not only relaxed the demand for optimal complementarity between Mtd and pert