Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist
Polina Isaikina, Ching‐Ju Tsai, Nikolaus Dietz, Filip Pamula, Anne Grahl, Kenneth N. Goldie, Ramón Guixà-González, Camila Branco, Marianne Paolini‐Bertrand, Nicolas Calo, Fabrice Cerini, Gebhard F. X. Schertler, Oliver Hartley, Henning Stahlberg, Timm Maier, Xavier Deupí, Stephan Grzesiek
Abstract
protein. The structure provides the rationale for the sequence-activity relation of agonist and antagonist chemokines. The N terminus of agonist chemokines pushes onto specific structural motifs at the bottom of the orthosteric pocket that activate the canonical GPCR microswitch network. This activation mechanism differs substantially from other CC chemokine receptors that bind chemokines with shorter N termini in a shallow binding mode involving unique sequence signatures and a specialized activation mechanism.