B 类 G 蛋白偶联受体的肽识别、信号转导和调节。

Peptide recognition, signaling and modulation of class B G protein-coupled receptors.

机构信息

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.

出版信息

Curr Opin Struct Biol. 2018 Aug;51:53-60. doi: 10.1016/j.sbi.2018.03.008. Epub 2018 Mar 19.

DOI:10.1016/j.sbi.2018.03.008

PMID:29567494

Abstract

Class B G protein-coupled receptors (GPCRs) are important drug targets in many human diseases, including type 2 diabetes, obesity, cardiovascular disease and neurodegeneration. Peptide hormones bind to these receptors through interactions with both the extracellular domain and transmembrane domain. Despite remarkable advances in structural studies of GPCRs, structural characterization of the full-length class B receptors remains extremely challenging due to their conformational complexity. The recently solved structures of class B GPCRs reveal the structural basis of peptide ligand recognition and modulation mechanisms of small molecule allosteric modulators. Furthermore, these structures provide essential insights into molecular mechanisms of class B GPCR signal transduction and modulation.

摘要

B 类 G 蛋白偶联受体（GPCRs）是许多人类疾病的重要药物靶点，包括 2 型糖尿病、肥胖症、心血管疾病和神经退行性疾病。肽激素通过与细胞外结构域和跨膜结构域的相互作用与这些受体结合。尽管 GPCRs 的结构研究取得了显著进展，但由于其构象复杂性，全长 B 类受体的结构特征仍然极具挑战性。最近解决的 B 类 GPCR 结构揭示了肽配体识别的结构基础和小分子变构调节剂的调控机制。此外，这些结构为 B 类 GPCR 信号转导和调节的分子机制提供了重要的见解。