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9uap

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cryo-EM structure of ligand-free active-state M1 muscarinic acetylcholine receptor with alpha5 helix of G11 protein complex

Structural highlights

9uap is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.62Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GNA11_HUMAN Phakomatosis cesioflammea;Uveal melanoma;Phakomatosis cesiomarmorata;Autosomal dominant hypocalcemia;Familial hypocalciuric hypercalcemia type 2;Cutis marmorata telangiectatica congenita. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

GNA11_HUMAN Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:31073061). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PubMed:31073061). Signaling by an activated GPCR promotes GDP release and GTP binding (PubMed:31073061). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:31073061). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:31073061). Signaling is mediated via phospholipase C-beta-dependent inositol lipid hydrolysis for signal propagation: activates phospholipase C-beta: following GPCR activation, GNA11 activates PLC-beta (PLCB1, PLCB2, PLCB3 or PLCB4), leading to production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) (PubMed:31073061). Transduces FFAR4 signaling in response to long-chain fatty acids (LCFAs) (PubMed:27852822). Together with GNAQ, required for heart development (By similarity).[UniProtKB:P21278]^[1] ^[2]

References

↑ Alvarez-Curto E, Inoue A, Jenkins L, Raihan SZ, Prihandoko R, Tobin AB, Milligan G. Targeted Elimination of G Proteins and Arrestins Defines Their Specific Contributions to Both Intensity and Duration of G Protein-coupled Receptor Signaling. J Biol Chem. 2016 Dec 30;291(53):27147-27159. PMID:27852822 doi:10.1074/jbc.M116.754887
↑ Maeda S, Qu Q, Robertson MJ, Skiniotis G, Kobilka BK. Structures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes. Science. 2019 May 10;364(6440):552-557. doi: 10.1126/science.aaw5188. PMID:31073061 doi:http://dx.doi.org/10.1126/science.aaw5188