Springael Jean-Yves, Urizar Eneko, Parmentier Marc
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium.
Cytokine Growth Factor Rev. 2005 Dec;16(6):611-23. doi: 10.1016/j.cytogfr.2005.05.005. Epub 2005 Jun 23.
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.
近年来越来越清楚的是，大多数（如果不是全部的话）G蛋白偶联受体（GPCR）能够形成二聚体或更高阶的寡聚体。趋化因子受体也不例外，CC和CXC受体均已证实存在同二聚化和异二聚化。功能分析表明二聚体的两个亚基之间存在负性结合协同作用。结果是只有一种趋化因子能够以高亲和力结合到受体二聚体上。在受体激活的背景下，这意味着激动剂结合引发的螺旋结构域运动在另一个原体中诱导相关变化。本文讨论了趋化因子二聚化过程在共受体功能和药物开发方面的影响。
