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Abstract：
A rich diversity of transmembrane G protein-coupled receptors (GPCRs) are used by eukaryotes to sense physical and chemical signals. In humans alone, 800 GPCRs comprise the largest and most therapeutically targeted receptor class. Recent advances in GPCR structural biology have produced hundreds of GPCR structures solved by X-ray diffraction and increasingly, cryo-electron microscopy (cryo-EM). Many of these structures are stabilized by site-specific cholesterol binding, but it is unclear whether these interactions are a product of recurring cholesterol-binding motifs and if observed patterns of cholesterol binding differ by experimental technique. Here, we comprehensively analyze the location and composition of cholesterol binding sites in the current set of 473 human GPCR structural chains. Our findings establish that cholesterol binds similarly in cryo-EM and X-ray structures and show that 92% of cholesterol molecules on GPCR surfaces reside in predictable locations that lack discernable cholesterol-binding motifs.
摘要：
真核生物使用丰富多样的跨膜G蛋白偶联受体(GPCRs)来感测物理和化学信号。仅在人类中，800个GPCR包含最大和最具治疗靶向性的受体类别。GPCR结构生物学的最新进展已经产生了数百个通过X射线衍射解决的GPCR结构，低温电子显微镜（cryo-EM）。这些结构中的许多都是通过位点特异性胆固醇结合来稳定的，但尚不清楚这些相互作用是否是胆固醇结合基序反复出现的产物，以及观察到的胆固醇结合模式是否因实验技术而异。这里,我们全面分析了当前473个人GPCR结构链中胆固醇结合位点的位置和组成.我们的发现确定了胆固醇在低温EM和X射线结构中的结合相似，并表明GPCR表面上92％的胆固醇分子位于缺乏可辨别的胆固醇结合基序的可预测位置。
