Successful Strategies to Determine High-Resolution Structures of GPCRs

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• 作者：Jin Xiang¹ ; ² ; Eugene Chun¹ ; Chang Liu¹ ; Liang Jing¹ ; Zina Al-Sahouri¹ ; Lan Zhu¹ ; Wei Liu¹ ; ^{w.liu@asu.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：GPCRs ; protein engineering ; ligand binding ; lipidic cubic phase ; structure-based drug discovery
• 刊名：Trends in Pharmacological Sciences
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：37
• 期：12
• 页码：1055-1069
• 全文大小：5116 K

文摘

G protein-coupled receptors (GPCRs) constitute the largest class of drug targets in the human genome, which highlights the importance of understanding the molecular basis of their activation, downstream signaling, and regulation. Since 2007, great progress has been made in the field of GPCR structure determination and their signaling complexes at the molecular level. Here, we summarize the high-resolution structures of over 30 different GPCRs with their co-crystallized ligands, and outline the successful strategies involved, including construct design, expression systems, and lipidic cubic phase (LCP) composition, and the many key technical parameters of the crystallization methods. By comparing the success rates of different strategies used in the past, we wish to pave the road for more successful structure–function research for GPCRs in the future.