title: Closing the ring: a fourth extracellular loop in chemokine receptors.
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.
authors.affiliation: Laboratory of Retrovirology, Public Research Centre for Health (CRP-Santé), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg.
authors.forename: Martyna
authors.initials: M
authors.lastname: Szpakowska
authors.affiliation: Laboratory of Retrovirology, Public Research Centre for Health (CRP-Santé), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg.
authors.forename: Danielle
authors.initials: D
authors.lastname: Perez Bercoff
authors.affiliation: Laboratory of Retrovirology, Public Research Centre for Health (CRP-Santé), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg. andy.chevigne@crp-sante.lu.
authors.forename: Andy
authors.initials: A
authors.lastname: Chevigné
mesh_terms: D018360:Crystallography, X-Ray; D004220:Disulfides; D006801:Humans; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000737:chemistry; D019718:Receptors, CXCR4 / Q000737:chemistry; D019707:Receptors, Chemokine / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry; D023062:Receptors, Interleukin-8A / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: C584933:CCR5 protein, human; C527276:CXCR4 protein, human; D004220:Disulfides; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D023062:Receptors, Interleukin-8A