7v9l | pdb_00007v9l

Cryo-EM structure of the SV1-Gs complex.

spinqualitylabelsall models 7v9l, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7v9l is a 5 chain structure with sequence from Bos taurus, Homo sapiens, Rattus norvegicus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.6Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9HB45_HUMAN Publication Abstract from PubMed Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone-releasing hormone receptor (GHRHR) is capable of transducing biased signal. Differing only at the receptor N terminus, GHRHR predominantly activates G(s) while SV1 selectively couples to beta-arrestins. Based on the cryogenic electron microscopy structures of SV1 in the apo state or GHRH-bound state in complex with the G(s) protein, molecular dynamics simulations reveal that the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, G(s) versus beta-arrestins. As suggested by mutagenesis and functional studies, it appears that GHRH-elicited signal bias toward beta-arrestin recruitment is constitutively mediated by SV1. The level of SV1 expression in prostate cancer cells is also positively correlated with ERK1/2 phosphorylation but negatively correlated with cAMP response. Our findings imply that constitutive signal bias may be a mechanism that ensures cancer cell proliferation. Constitutive signal bias mediated by the human GHRHR splice variant 1.,Cong Z, Zhou F, Zhang C, Zou X, Zhang H, Wang Y, Zhou Q, Cai X, Liu Q, Li J, Shao L, Mao C, Wang X, Wu J, Xia T, Zhao LH, Jiang H, Zhang Y, Xu HE, Cheng X, Yang D, Wang MW Proc Natl Acad Sci U S A. 2021 Oct 5;118(40):e2106606118. doi: , 10.1073/pnas.2106606118. PMID:34599099 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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