7w0n
From Proteopedia
Cryo-EM structure of a dimeric GPCR-Gi complex with peptide
Structural highlights
Function[GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.[1] [2] 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Escherichia coli | Homo sapiens | Large Structures | Hanson M | Liu LE | Wu LJ | Xu F | Yue Y