skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?

Abstract

Chemokines and their cell surface G protein–coupled receptors are critical for cell migration, not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provided unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs. In parallel, chemokine receptor structures with small molecules reveal the complicated and diverse structural foundations of small molecule antagonism and allostery, highlight the inherent physicochemical challenges of receptor:chemokine interfaces, and suggest novel epitopes that can be exploited to overcome these challenges. The structures and models promote unique understanding of chemokine receptor biology, including the interpretation of two decades of experimental studies, and will undoubtedly assist future drug discovery endeavors.

Authors:
 [1];  [1];  [1];  [1];  [1]
  1. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093,,
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1372231
Resource Type:
Journal Article
Resource Relation:
Journal Name: Annual Review of Biophysics; Journal Volume: 46; Journal Issue: 1
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Kufareva, Irina, Gustavsson, Martin, Zheng, Yi, Stephens, Bryan S., and Handel, Tracy M. What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?. United States: N. p., 2017. Web. doi:10.1146/annurev-biophys-051013-022942.
Kufareva, Irina, Gustavsson, Martin, Zheng, Yi, Stephens, Bryan S., & Handel, Tracy M. What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?. United States. doi:10.1146/annurev-biophys-051013-022942.
Kufareva, Irina, Gustavsson, Martin, Zheng, Yi, Stephens, Bryan S., and Handel, Tracy M. Mon . "What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?". United States. doi:10.1146/annurev-biophys-051013-022942.
@article{osti_1372231,
title = {What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?},
author = {Kufareva, Irina and Gustavsson, Martin and Zheng, Yi and Stephens, Bryan S. and Handel, Tracy M.},
abstractNote = {Chemokines and their cell surface G protein–coupled receptors are critical for cell migration, not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provided unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs. In parallel, chemokine receptor structures with small molecules reveal the complicated and diverse structural foundations of small molecule antagonism and allostery, highlight the inherent physicochemical challenges of receptor:chemokine interfaces, and suggest novel epitopes that can be exploited to overcome these challenges. The structures and models promote unique understanding of chemokine receptor biology, including the interpretation of two decades of experimental studies, and will undoubtedly assist future drug discovery endeavors.},
doi = {10.1146/annurev-biophys-051013-022942},
journal = {Annual Review of Biophysics},
number = 1,
volume = 46,
place = {United States},
year = {Mon May 22 00:00:00 EDT 2017},
month = {Mon May 22 00:00:00 EDT 2017}
}