Details

Autor(en) / Beteiligte

• Ma, Yingli
• Yue, Yang
• Ma, Yanbin
• Zhang, Qing
• Zhou, Qingtong
• Song, Yunpeng
• Shen, Yuqing
• Li, Xun
• Ma, Xiaochuan
• Li, Chao
• Hanson, Michael A.
• Han, Gye Won
• Sickmier, E. Allen
• Swaminath, Gayathri
• Zhao, Suwen
• Stevens, Raymond C.
• Hu, Liaoyuan A.
• Zhong, Wenge
• Zhang, Mingqiang
• Xu, Fei

Titel

Structural Basis for Apelin Control of the Human Apelin Receptor

Ist Teil von

• Structure (London), 2017-06, Vol.25 (6), p.858-866.e4

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Apelin receptor (APJR) is a key regulator of human cardiovascular function and is activated by two different endogenous peptide ligands, apelin and Elabela, each with different isoforms diversified by length and amino acid sequence. Here we report the 2.6-Å resolution crystal structure of human APJR in complex with a designed 17-amino-acid apelin mimetic peptide agonist. The structure reveals that the peptide agonist adopts a lactam constrained curved two-site ligand binding mode. Combined with mutation analysis and molecular dynamics simulations with apelin-13 binding to the wild-type APJR, this structure provides a mechanistic understanding of apelin recognition and binding specificity. Comparison of this structure with that of other peptide receptors suggests that endogenous peptide ligands with a high degree of conformational flexibility may bind and modulate the receptors via a similar two-site binding mechanism. [Display omitted] •Designed peptide mimic AMG3054 with reduced conformational flexibility•Structure of apelin receptor in complex with AMG3054•Designed peptide AMG3054 adopts a lactam constrained curved structure•A two-site binding mode is observed for peptide GPCR recognition Ma et al. present an atomic-resolution structure of the human apelin receptor (APJR, a class A G-protein-coupled receptor) in complex with a 17-residue apelin peptide mimic by X-ray crystallography. This structure reveals a two-site ligand binding mode that has not been seen in any other solved class A receptor structures.