Rajagopalan Lavanya, Rajarathnam Krishna
Department of Biochemistry and Molecular Biology and Sealy Center for Structural Biology, The University of Texas Medical Branch, Galveston, TX 77555-1055, USA.
Biosci Rep. 2006 Oct;26(5):325-39. doi: 10.1007/s10540-006-9025-9.
Chemokine receptors play fundamental roles in human physiology from embryogenesis to inflammatory response. The receptors belong to the G-protein coupled receptor class, and are activated by chemokine ligands with a range of specificities and affinities that result in a complicated network of interactions. The molecular basis for function is largely a black box, and can be directly attributed to the lack of structural information on the receptors. Studies to date indicate that function can be best described by a two-site model, that involves interactions between the receptor N-domain and ligand N-terminal loop residues (site-I), and between receptor extracellular loop and the ligand N-terminal residues (site-II). In this review, we describe how the two-site model could modulate binding affinity and ligand selectivity, and also highlight some of the unique chemokine receptor features, and their role in function.
趋化因子受体在从胚胎发生到炎症反应的人类生理过程中发挥着重要作用。这些受体属于G蛋白偶联受体类别，被具有一系列特异性和亲和力的趋化因子配体激活，从而形成一个复杂的相互作用网络。其功能的分子基础在很大程度上仍是未知领域，这直接归因于缺乏关于这些受体的结构信息。迄今为止的研究表明，功能最好用双位点模型来描述，该模型涉及受体N结构域与配体N端环残基之间的相互作用（位点I），以及受体细胞外环与配体N端残基之间的相互作用（位点II）。在这篇综述中，我们描述了双位点模型如何调节结合亲和力和配体选择性，还强调了一些趋化因子受体的独特特征及其在功能中的作用。
