TY - JOUR
T1 - Parallel Evolution of Chemokine Binding by Structurally Related Herpesvirus Decoy Receptors
AU - Lubman, Olga Y.
AU - Fremont, Daved H.
N1 - Funding Information:
The authors would like to thank J. Nix at ALS beamline 4.2.2 (Lawrence Berkeley Laboratories) for help with X-ray data collection, and the APS CCP4 School for help with iodide anomalous signal calculation and data collection at macromolecular crystallography beamline 23ID-D. We thank Chris Nelson for discussions and careful reading of the manuscript. This work was supported by the Washington University/Pfizer Biomedical Agreement , the Center for Women's Infectious Disease Research (cWIDR) , and NIAID grants R01 AI019687 and U54 AI057160 .
Publisher Copyright:
© 2016 Elsevier Ltd. All rights reserved.
PY - 2016/1/5
Y1 - 2016/1/5
N2 - 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. 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.
AB - 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. 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.
UR - http://www.scopus.com/inward/record.url?scp=84953289345&partnerID=8YFLogxK
U2 - 10.1016/j.str.2015.10.018
DO - 10.1016/j.str.2015.10.018
M3 - Article
C2 - 26671708
AN - SCOPUS:84953289345
VL - 24
SP - 57
EP - 69
JO - Structure
JF - Structure
SN - 0969-2126
IS - 1
ER -