PDF(Pubmed)
Abstract：
G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs; however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of class C GPCRs and speculate on their corresponding therapeutic potential.
摘要：
G蛋白偶联受体（GPCRs），最大的细胞表面受体超家族之一，是七螺旋整合膜蛋白，在几乎每个器官系统中起关键作用。G蛋白偶联受体在富含胆固醇的细胞膜上起作用，GPCR跨膜结构域附近的胆固醇水平失衡影响许多GPCRs的结构和/或功能，与几种疾病相关的现象。胆固醇的这些作用可以通过改变脂质环境的机械特性而导致间接变化，或者通过与蛋白质上的特定位点结合而导致直接变化。有许多关于胆固醇如何调节A类GPCRs的研究和评论；然而，C类GPCR的这一研究领域尚待探索，其特征在于大的细胞外区域并且通常形成组成型二聚体。这篇评论强调了互动的具体地点，功能,和C类GPCRs的胆固醇识别所涉及的结构动力学。我们总结了一些典型家族成员的最新数据，以解释膜胆固醇对C类GPCRs结构特征和功能的影响，并推测其相应的治疗潜力。
