Selective ligand recognition by a diversity-generating retroelement variable protein.

Autor: Jason L Miller, Johanne Le Coq, Asher Hodes, Roman Barbalat, Jeff F Miller, Partho Ghosh
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: PLoS Biology, Vol 6, Iss 6, p e131 (2008)
Druh dokumentu: article
ISSN: 1544-9173
1545-7885
DOI: 10.1371/journal.pbio.0060131
Popis: 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 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.
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