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Nanobodies to Study G Protein–Coupled Receptor Structure and Function
Annual Review of Pharmacology and Toxicology ( IF 11.2 ) Pub Date : 2017-01-06 00:00:00 , DOI: 10.1146/annurev-pharmtox-010716-104710
Aashish Manglik 1 , Brian K Kobilka 1 , Jan Steyaert 2, 3
Affiliation  

Ligand-induced activation of G protein–coupled receptors (GPCRs) is a key mechanism permitting communication between cells and organs. Enormous progress has recently elucidated the structural and dynamic features of GPCR transmembrane signaling. Nanobodies, the recombinant antigen–binding fragments of camelid heavy-chain-only antibodies, have emerged as important research tools to lock GPCRs in particular conformational states. Active-state stabilizing nanobodies have elucidated several agonist-bound structures of hormone-activated GPCRs and have provided insight into the dynamic character of receptors. Nanobodies have also been used to stabilize transient GPCR transmembrane signaling complexes, yielding the first structural insights into GPCR signal transduction across the cellular membrane. Beyond their in vitro uses, nanobodies have served as conformational biosensors in living systems and have provided novel ways to modulate GPCR function. Here, we highlight several examples of how nanobodies have enabled the study of GPCR function and give insights into potential future uses of these important tools.

中文翻译:



研究 G 蛋白偶联受体结构和功能的纳米抗体



配体诱导的 G 蛋白偶联受体 (GPCR) 激活是细胞和器官之间通讯的关键机制。最近在阐明 GPCR 跨膜信号传导的结构和动态特征方面取得了巨大进展。纳米抗体是骆驼科动物纯重链抗体的重组抗原结合片段,已成为将 GPCR 锁定在特定构象状态的重要研究工具。活性状态稳定纳米抗体已经阐明了激素激活的 GPCR 的几种激动剂结合结构,并提供了对受体动态特性的深入了解。纳米抗体也已被用于稳定瞬时 GPCR 跨膜信号复合物,从而首次对跨细胞膜的 GPCR 信号转导产生了结构见解。除了体外用途之外,纳米抗体还可以作为生命系统中的构象生物传感器,并提供调节 GPCR 功能的新方法。在这里,我们重点介绍了纳米抗体如何支持 GPCR 功能研究的几个例子,并深入探讨了这些重要工具的未来潜在用途。

更新日期:2017-01-06
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