CCR5 Mutations Distinguish N-Terminal Modifications of RANTES (CCL5) with Agonist versus Antagonist Activity.

Won-Tak Choi (1) , Rebecca Nedellec (1) , Mia Coetzer (1) , Philippe Colin (2, 3) , Bernard Lagane (2) , Robin E Offord (4) , Oliver Hartley (5) , Donald E Mosier (1)

1 Department of Immunology and Microbial Science
2 Pathogénie Virale
3 UPD7 - Université Paris Diderot - Paris 7
4 Mintaka Foundation
5 Department of Structural Biology and Bioinformatics

CCR5 is the major HIV-1 entry coreceptor. RANTES/CCL5 analogs are more potent inhibitors of infection than native chemokines; one class activates and internalizes CCR5, one neither activates nor internalizes, and a third partially internalizes without activation. Here we show that mutations in CCR5 transmembrane domains differentially impact the activity of these three inhibitor classes, suggesting that the transmembrane region of CCR5, a key interaction site for inhibitors, is a sensitive molecular switch, modulating receptor activity.

Domaines: Virologie

Won-Tak Choi, Rebecca Nedellec, Mia Coetzer, Philippe Colin, Bernard Lagane, et al.. CCR5 Mutations Distinguish N-Terminal Modifications of RANTES (CCL5) with Agonist versus Antagonist Activity.. Journal of Virology, 2012, 86 (18), pp.10218-20. ⟨10.1128/JVI.00353-12⟩. ⟨pasteur-00731737⟩