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Structural Basis for Apelin Control of the Human Apelin Receptor
- Source :
- Structure. 25:858-866.e4
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
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.
- Subjects :
- 0301 basic medicine
Agonist
Protein Conformation
medicine.drug_class
Peptide
Molecular Dynamics Simulation
Crystallography, X-Ray
Peptides, Cyclic
03 medical and health sciences
Structural Biology
medicine
Humans
Receptor
Molecular Biology
Peptide sequence
Binding selectivity
Apelin receptor
chemistry.chemical_classification
Apelin Receptors
Alanine
030102 biochemistry & molecular biology
Molecular Mimicry
Peptide Fragments
Amino acid
Cell biology
Apelin
030104 developmental biology
Biochemistry
chemistry
Mutagenesis, Site-Directed
Signal Transduction
Subjects
Details
- ISSN :
- 09692126
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Structure
- Accession number :
- edsair.doi.dedup.....726840d74c9fd8b786372c03f12f8db8