7sus
From Proteopedia
Crystal structure of Apelin receptor in complex with small molecule
Structural highlights
FunctionAPJ_HUMAN Receptor for apelin coupled to G proteins that inhibit adenylate cyclase activity. Alternative coreceptor with CD4 for HIV-1 infection; may be involved in the development of AIDS dementia.RUBR_CLOPA Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule. Publication Abstract from PubMedThe technique of cryogenic-electron microscopy (cryo-EM) has revolutionized the field of membrane protein structure and function with a focus on the dominantly observed molecular species. This report describes the structural characterization of a fully active human apelin receptor (APJR) complexed with heterotrimeric G protein observed in both 2:1 and 1:1 stoichiometric ratios. We use cryo-EM single-particle analysis to determine the structural details of both species from the same sample preparation. Protein preparations, in the presence of the endogenous peptide ligand ELA or a synthetic small molecule, both demonstrate these mixed stoichiometric states. Structural differences in G protein engagement between dimeric and monomeric APJR suggest a role for the stoichiometry of G protein-coupled receptor- (GPCR-)G protein coupling on downstream signaling and receptor pharmacology. Furthermore, a small, hydrophobic dimer interface provides a starting framework for additional class A GPCR dimerization studies. Together, these findings uncover a mechanism of versatile regulation through oligomerization by which GPCRs can modulate their signaling. Structural insight into apelin receptor-G protein stoichiometry.,Yue Y, Liu L, Wu LJ, Wu Y, Wang L, Li F, Liu J, Han GW, Chen B, Lin X, Brouillette RL, Breault E, Longpre JM, Shi S, Lei H, Sarret P, Stevens RC, Hanson MA, Xu F Nat Struct Mol Biol. 2022 Jul;29(7):688-697. doi: 10.1038/s41594-022-00797-5., Epub 2022 Jul 11. PMID:35817871[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Clostridium pasteurianum | Homo sapiens | Large Structures | Han GW | Hanson M | Liu LE | Xu F | Yue Y