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Title: Parallel Evolution of Chemokine Binding by Structurally Related Herpesvirus Decoy Receptors

Abstract

A wide variety of pathogens targets chemokine signaling networks in order to disrupt host immune surveillance and defense. Here, we report a structural and mutational analysis of rodent herpesvirus Peru encoded R17, a potent chemokine inhibitor that sequesters CC and C chemokines with high affinity. R17 consists of a pair of β-sandwich domains linked together by a bridging sheet, which form an acidic binding cleft for the chemokine CCL3 on the opposite face of a basic surface cluster that binds glycosaminoglycans. R17 promiscuously engages chemokines primarily through the same N-loop determinants used for host receptor recognition while residues located in the chemokine 40s loop drive kinetically stable complex formation. Here, the core fold adopted by R17 is unexpectedly similar to that of the M3 chemokine decoy receptor encoded by MHV-68, although, strikingly, neither the location of ligand engagement nor the stoichiometry of binding is conserved, suggesting that their functions evolved independently.

Authors:
 [1];  [1]
  1. Washington Univ. School of Medicine, St. Louis, MO (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
NIAID
OSTI Identifier:
1237760
Grant/Contract Number:  
R01 AI019687; U54 AI057160
Resource Type:
Accepted Manuscript
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 24; Journal Issue: 1; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Lubman, Olga Y., and Fremont, Daved H. Parallel Evolution of Chemokine Binding by Structurally Related Herpesvirus Decoy Receptors. United States: N. p., 2015. Web. https://doi.org/10.1016/j.str.2015.10.018.
Lubman, Olga Y., & Fremont, Daved H. Parallel Evolution of Chemokine Binding by Structurally Related Herpesvirus Decoy Receptors. United States. https://doi.org/10.1016/j.str.2015.10.018
Lubman, Olga Y., and Fremont, Daved H. Thu . "Parallel Evolution of Chemokine Binding by Structurally Related Herpesvirus Decoy Receptors". United States. https://doi.org/10.1016/j.str.2015.10.018. https://www.osti.gov/servlets/purl/1237760.
@article{osti_1237760,
title = {Parallel Evolution of Chemokine Binding by Structurally Related Herpesvirus Decoy Receptors},
author = {Lubman, Olga Y. and Fremont, Daved H.},
abstractNote = {A wide variety of pathogens targets chemokine signaling networks in order to disrupt host immune surveillance and defense. Here, we report a structural and mutational analysis of rodent herpesvirus Peru encoded R17, a potent chemokine inhibitor that sequesters CC and C chemokines with high affinity. R17 consists of a pair of β-sandwich domains linked together by a bridging sheet, which form an acidic binding cleft for the chemokine CCL3 on the opposite face of a basic surface cluster that binds glycosaminoglycans. R17 promiscuously engages chemokines primarily through the same N-loop determinants used for host receptor recognition while residues located in the chemokine 40s loop drive kinetically stable complex formation. Here, the core fold adopted by R17 is unexpectedly similar to that of the M3 chemokine decoy receptor encoded by MHV-68, although, strikingly, neither the location of ligand engagement nor the stoichiometry of binding is conserved, suggesting that their functions evolved independently.},
doi = {10.1016/j.str.2015.10.018},
journal = {Structure},
number = 1,
volume = 24,
place = {United States},
year = {2015},
month = {12}
}

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