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

Publikation: Bidrag til tidsskriftReviewForskningfagfællebedømt

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.

OriginalsprogEngelsk
TidsskriftAnnual Review of Biophysics
Vol/bind46
Sider (fra-til)175-198
Antal sider24
ISSN1936-122X
DOI
StatusUdgivet - 22 maj 2017
Eksternt udgivetJa

ID: 329432662