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Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor

Viruses have evolved a myriad of evasion strategies focused on undermining chemokine-mediated immune surveillance, exemplified by the mouse γ-herpesvirus 68 M3 decoy receptor. Crystal structures of M3 in complex with C chemokine ligand 1/lymphotactin and CC chemokine ligand 2/monocyte chemoattractan...

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Detalles Bibliográficos
Autores principales: Alexander-Brett, Jennifer M., Fremont, Daved H.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150966/
https://www.ncbi.nlm.nih.gov/pubmed/18070938
http://dx.doi.org/10.1084/jem.20071677
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author Alexander-Brett, Jennifer M.
Fremont, Daved H.
author_facet Alexander-Brett, Jennifer M.
Fremont, Daved H.
author_sort Alexander-Brett, Jennifer M.
collection PubMed
description Viruses have evolved a myriad of evasion strategies focused on undermining chemokine-mediated immune surveillance, exemplified by the mouse γ-herpesvirus 68 M3 decoy receptor. Crystal structures of M3 in complex with C chemokine ligand 1/lymphotactin and CC chemokine ligand 2/monocyte chemoattractant protein 1 reveal that invariant chemokine features associated with G protein–coupled receptor binding are primarily recognized by the decoy C-terminal domain, whereas the N-terminal domain (NTD) reconfigures to engage divergent basic residue clusters on the surface of chemokines. Favorable electrostatic forces dramatically enhance the association kinetics of chemokine binding by M3, with a primary role ascribed to acidic NTD regions that effectively mimic glycosaminoglycan interactions. Thus, M3 employs two distinct mechanisms of chemical imitation to potently sequester chemokines, thereby inhibiting chemokine receptor binding events as well as the formation of chemotactic gradients necessary for directed leukocyte trafficking.
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spelling pubmed-21509662008-06-24 Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor Alexander-Brett, Jennifer M. Fremont, Daved H. J Exp Med Articles Viruses have evolved a myriad of evasion strategies focused on undermining chemokine-mediated immune surveillance, exemplified by the mouse γ-herpesvirus 68 M3 decoy receptor. Crystal structures of M3 in complex with C chemokine ligand 1/lymphotactin and CC chemokine ligand 2/monocyte chemoattractant protein 1 reveal that invariant chemokine features associated with G protein–coupled receptor binding are primarily recognized by the decoy C-terminal domain, whereas the N-terminal domain (NTD) reconfigures to engage divergent basic residue clusters on the surface of chemokines. Favorable electrostatic forces dramatically enhance the association kinetics of chemokine binding by M3, with a primary role ascribed to acidic NTD regions that effectively mimic glycosaminoglycan interactions. Thus, M3 employs two distinct mechanisms of chemical imitation to potently sequester chemokines, thereby inhibiting chemokine receptor binding events as well as the formation of chemotactic gradients necessary for directed leukocyte trafficking. The Rockefeller University Press 2007-12-24 /pmc/articles/PMC2150966/ /pubmed/18070938 http://dx.doi.org/10.1084/jem.20071677 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Alexander-Brett, Jennifer M.
Fremont, Daved H.
Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor
title Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor
title_full Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor
title_fullStr Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor
title_full_unstemmed Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor
title_short Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor
title_sort dual gpcr and gag mimicry by the m3 chemokine decoy receptor
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150966/
https://www.ncbi.nlm.nih.gov/pubmed/18070938
http://dx.doi.org/10.1084/jem.20071677
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