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Publication Abstract from PubMed

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-A 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.

Structural Basis for Apelin Control of the Human Apelin Receptor.,Ma Y, Yue Y, Ma Y, Zhang Q, Zhou Q, Song Y, Shen Y, Li X, Ma X, Li C, Hanson MA, Han GW, Sickmier EA, Swaminath G, Zhao S, Stevens RC, Hu LA, Zhong W, Zhang M, Xu F Structure. 2017 Jun 6;25(6):858-866.e4. doi: 10.1016/j.str.2017.04.008. Epub 2017, May 18. PMID:28528775^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.