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

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 bac...

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Main Authors: Jason L Miller, Johanne Le Coq, Asher Hodes, Roman Barbalat, Jeff F Miller, Partho Ghosh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-06-01
Series:PLoS Biology
Online Access:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0060131&type=printable
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author Jason L Miller
Johanne Le Coq
Asher Hodes
Roman Barbalat
Jeff F Miller
Partho Ghosh
author_facet Jason L Miller
Johanne Le Coq
Asher Hodes
Roman Barbalat
Jeff F Miller
Partho Ghosh
author_sort Jason L Miller
collection DOAJ
description 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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publishDate 2008-06-01
publisher Public Library of Science (PLoS)
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spelling doaj-art-1705d6f2babb4c68b4ef80c4f69442e32025-08-20T02:02:44ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852008-06-0166e13110.1371/journal.pbio.0060131Selective ligand recognition by a diversity-generating retroelement variable protein.Jason L MillerJohanne Le CoqAsher HodesRoman BarbalatJeff F MillerPartho GhoshDiversity-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.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0060131&type=printable
spellingShingle Jason L Miller
Johanne Le Coq
Asher Hodes
Roman Barbalat
Jeff F Miller
Partho Ghosh
Selective ligand recognition by a diversity-generating retroelement variable protein.
PLoS Biology
title Selective ligand recognition by a diversity-generating retroelement variable protein.
title_full Selective ligand recognition by a diversity-generating retroelement variable protein.
title_fullStr Selective ligand recognition by a diversity-generating retroelement variable protein.
title_full_unstemmed Selective ligand recognition by a diversity-generating retroelement variable protein.
title_short Selective ligand recognition by a diversity-generating retroelement variable protein.
title_sort selective ligand recognition by a diversity generating retroelement variable protein
url https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0060131&type=printable
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