7ewp | pdb_00007ewp

Cryo-EM structure of human GPR158 in complex with RGS7-Gbeta5 in a 2:1:1 ratio

spinqualitylabelsall models 7ewp, resolution 4.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ewp is a 4 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 4.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GNB5_HUMAN GNB5-related intellectual disability-cardiac arrhythmia syndrome. 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 GNB5_HUMAN Enhances GTPase-activating protein (GAP) activity of regulator of G protein signaling (RGS) proteins, such as RGS7 and RGS9, hence involved in the termination of the signaling initiated by the G protein coupled receptors (GPCRs) by accelerating the GTP hydrolysis on the G-alpha subunits, thereby promoting their inactivation (PubMed:27677260). Increases RGS7 GTPase-activating protein (GAP) activity, thereby regulating mood and cognition (By similarity). Increases RGS9 GTPase-activating protein (GAP) activity, hence contributes to the deactivation of G protein signaling initiated by D(2) dopamine receptors (PubMed:27677260). May play an important role in neuronal signaling, including in the parasympathetic, but not sympathetic, control of heart rate (By similarity).[UniProtKB:A1L271][UniProtKB:P62881] Publication Abstract from PubMed GPR158, a class C orphan GPCR, functions in cognition, stress-induced mood control, and synaptic development. Among class C GPCRs, GPR158 is unique as it lacks a Venus flytrap-fold ligand-binding domain and terminates Galphai/o protein signaling through the RGS7-Gbeta5 heterodimer. Here, we report the cryo-EM structures of GPR158 alone and in complex with one or two RGS7-Gbeta5 heterodimers. GPR158 dimerizes through Per-Arnt-Sim-fold extracellular and transmembrane (TM) domains connected by an epidermal growth factor-like linker. The TM domain (TMD) reflects both inactive and active states of other class C GPCRs: a compact intracellular TMD, conformations of the two intracellular loops (ICLs) and the TMD interface formed by TM4/5. The ICL2, ICL3, TM3, and first helix of the cytoplasmic coiled-coil provide a platform for the DHEX domain of one RGS7 and the second helix recruits another RGS7. The unique features of the RGS7-binding site underlie the selectivity of GPR158 for RGS7. Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gbeta5.,Jeong E, Kim Y, Jeong J, Cho Y Nat Commun. 2021 Nov 23;12(1):6805. doi: 10.1038/s41467-021-27147-1. PMID:34815401 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Regulator of G-protein signaling 3D structures Transducin 3D structures

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