7yon

Publication Abstract from PubMed

Neuropeptide Y (NPY) and its receptors are expressed in various human tissues including the brain where they regulate appetite and emotion. Upon NPY stimulation, the neuropeptide Y1 and Y2 receptors (Y(1)R and Y(2)R, respectively) activate G(I) signaling, but their physiological responses to food intake are different. In addition, deletion of the two N-terminal amino acids of peptide YY (PYY(3-36)), the endogenous form found in circulation, can stimulate Y(2)R but not Y(1)R, suggesting that Y(1)R and Y(2)R may have distinct ligand-binding modes. Here, we report the cryo-electron microscopy structures of the PYY(3-36)‒Y(2)R‒G(i) and NPY‒Y(2)R‒G(i) complexes. Using cell-based assays, molecular dynamics simulations, and structural analysis, we revealed the molecular basis of the exclusive binding of PYY(3-36) to Y(2)R. Furthermore, we demonstrated that Y(2)R favors G protein signaling over beta-arrestin signaling upon activation, whereas Y(1)R does not show a preference between these two pathways.

Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling.,Kang H, Park C, Choi YK, Bae J, Kwon S, Kim J, Choi C, Seok C, Im W, Choi HJ Structure. 2023 Jan 5;31(1):44-57.e6. doi: 10.1016/j.str.2022.11.010. Epub 2022 , Dec 15. PMID:36525977^[3]

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