Dimerization of chemokine receptors and its functional consequences.
It became clear over the recent years that most, if not all, G protein-coupled receptors (GPCR) are able to form dimers or higher order oligomers. Chemokine receptors make no exception to this new rule and both homo- and heterodimerization were demonstrated for CC and CXC receptors. Functional analyses demonstrated negative binding cooperativity between the two subunits of a dimer. The consequence is that only one chemokine can bind with high affinity onto a receptor dimer. In the context of receptor activation, this implies that the motions of helical domains triggered by the binding of agonists induce correlated changes in the other protomer. The impact of the chemokine dimerization process in terms of co-receptor function and drug development is discussed.
Springael
Jean-Yves
JY
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium.
Urizar
Eneko
E
Parmentier
Marc
M
D000818:Animals; D019281:Dimerization; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000502:physiology*
D019707:Receptors, Chemokine