PerspectiveGPCRs

Closing the Ring: A Fourth Extracellular Loop in Chemokine Receptors

See allHide authors and affiliations

Sci. Signal.  02 Sep 2014:
Vol. 7, Issue 341, pp. pe21
DOI: 10.1126/scisignal.2005664

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Abstract

Chemokine receptors are heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCR) that play fundamental roles in many physiological and pathological processes. Typically, these receptors form a seven-transmembrane helix bundle, which is stabilized by a disulfide bond bridging the top of the third transmembrane segment (TM3) and the second extracellular loop (ECL2). Resolution of the three-dimensional structures of the chemokine receptors CXCR1, CXCR4, and CCR5 revealed the existence of a second disulfide bridge that links the N terminus of the receptor to the top of the seventh transmembrane segment (TM7), thereby closing the receptor into a ring. An important consequence of this second disulfide bond is the formation of an additional extracellular loop, which shapes the entrance of the ligand-binding pocket and adds rigidity to the overall surface of the receptor. Here, we discuss the features of these “pseudo-loops,” the structural requirements for their formation, and the effects they may have on receptor function.

View Full Text