7f9y

From Proteopedia
Jump to navigation Jump to search

ghrelin-bound ghrelin receptor in complex with Gqghrelin-bound ghrelin receptor in complex with Gq

Structural highlights

7f9y is a 6 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.9Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GHSR_HUMAN Short stature due to GHSR deficiency. The disease is caused by variants affecting the gene represented in this entry.

Function

C562_ECOLX Electron-transport protein of unknown function.GHSR_HUMAN Receptor for ghrelin, coupled to G-alpha-11 proteins. Stimulates growth hormone secretion. Binds also other growth hormone releasing peptides (GHRP) (e.g. Met-enkephalin and GHRP-6) as well as non-peptide, low molecular weight secretagogues (e.g. L-692,429, MK-0677, adenosine).[1] [2]

Publication Abstract from PubMed

Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of G(q)-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.

Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor.,Wang Y, Guo S, Zhuang Y, Yun Y, Xu P, He X, Guo J, Yin W, Xu HE, Xie X, Jiang Y Nat Commun. 2021 Aug 20;12(1):5064. doi: 10.1038/s41467-021-25364-2. PMID:34417468[3]

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

See Also

References

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999 Dec 9;402(6762):656-60. PMID:10604470 doi:http://dx.doi.org/10.1038/45230
  2. Smith RG, Leonard R, Bailey AR, Palyha O, Feighner S, Tan C, Mckee KK, Pong SS, Griffin P, Howard A. Growth hormone secretagogue receptor family members and ligands. Endocrine. 2001 Feb;14(1):9-14. PMID:11322507 doi:http://dx.doi.org/ENDO:14:1:009
  3. Wang Y, Guo S, Zhuang Y, Yun Y, Xu P, He X, Guo J, Yin W, Xu HE, Xie X, Jiang Y. Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor. Nat Commun. 2021 Aug 20;12(1):5064. PMID:34417468 doi:10.1038/s41467-021-25364-2

7f9y, resolution 2.90Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA