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 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)âY(2)RâG(i) and NPYâY(2)RâG(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.
References
- ↑ Cho H, Kehrl JH. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007 Jul 16;178(2):245-55. PMID:17635935 doi:10.1083/jcb.200604114
- ↑ Johnston CA, Siderovski DP. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. PMID:17264214
- ↑ Kang H, Park C, Choi YK, Bae J, Kwon S, Kim J, Choi C, Seok C, Im W, Choi HJ. Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling. Structure. 2023 Jan 5;31(1):44-57.e6. PMID:36525977 doi:10.1016/j.str.2022.11.010
