5VBL

Structure of apelin receptor in complex with agonist peptide

5VBL の概要

• エントリーDOI: 10.2210/pdb5vbl/pdb
• 分子名称: agonist peptide, Apelin receptor,Rubredoxin,Apelin receptor Chimera, ZINC ION, ... (5 entities in total)
• 機能のキーワード: human apelin receptor complex, agonist peptide, amg3054, gpcr, rubredoxin, membrane protein, lcp, synchrotron radiation, peptide-gcpr recognition, cardiovascular drug target, specific recognition, binding specificity, designed agonist peptide mimic, isopeptide
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell membrane : P35414
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49248.92

構造登録者

Ma, Y.,Yue, Y.,Ma, Y.,Zhang, Q.,Zhou, Q.,Song, Y.,Shen, Y.,Li, X.,Ma, X.,Li, C.,Hanson, M.A.,Han, G.W.,Sickmier, E.A.,Swaminath, G.,Zhao, S.,Stevems, R.C.,Hu, L.A.,Zhong, W.,Zhang, M.,Xu, F. (登録日: 2017-03-29, 公開日: 2017-05-31, 最終更新日: 2023-11-15)

主引用文献

Ma, Y.,Yue, Y.,Ma, Y.,Zhang, Q.,Zhou, Q.,Song, Y.,Shen, Y.,Li, X.,Ma, X.,Li, C.,Hanson, M.A.,Han, G.W.,Sickmier, E.A.,Swaminath, G.,Zhao, S.,Stevens, R.C.,Hu, L.A.,Zhong, W.,Zhang, M.,Xu, F.
Structural Basis for Apelin Control of the Human Apelin Receptor
Structure, 25:858-866.e4, 2017

PubMed Abstract: 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.

PubMed: 28528775
DOI: 10.1016/j.str.2017.04.008

実験手法

X-RAY DIFFRACTION (2.6 Å)