6vu5

Structure of G-alpha-q bound to its chaperone Ric-8A

spinqualitylabelsall models 6vu5, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vu5 is a 2 chain structure with sequence from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.5Å Ligands: SEP, TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RIC8A_RAT Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins. Able to activate GNAI1, GNAO1 and GNAQ, but not GNAS by exchanging bound GDP for free GTP. Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein, possibly leading to release G(i)-alpha-GTP and NuMA proteins from the NuMA-GPSM2-G(i)-alpha-GDP complex. Also acts as an activator for G(q)-alpha (GNAQ) protein by enhancing the G(q)-coupled receptor-mediated ERK activation. Publication Abstract from PubMed Many chaperones promote nascent polypeptide folding followed by substrate release through ATP-dependent conformational changes. Here we show cryoEM structures of Galpha subunit folding intermediates in complex with full-length Ric-8A, a unique chaperone-client system in which substrate release is facilitated by guanine nucleotide binding to the client G protein. The structures of Ric-8A-Galphai and Ric-8A-Galphaq complexes reveal that the chaperone employs its extended C-terminal region to cradle the Ras-like domain of Galpha, positioning the Ras core in contact with the Ric-8A core while engaging its switch2 nucleotide binding region. The C-terminal alpha5 helix of Galpha is held away from the Ras-like domain through Ric-8A core domain interactions, which critically depend on recognition of the Galpha C terminus by the chaperone. The structures, complemented with biochemical and cellular chaperoning data, support a folding quality control mechanism that ensures proper formation of the C-terminal alpha5 helix before allowing GTP-gated release of Galpha from Ric-8A. Structures of Galpha Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms.,Seven AB, Hilger D, Papasergi-Scott MM, Zhang L, Qu Q, Kobilka BK, Tall GG, Skiniotis G Cell Rep. 2020 Feb 28. pii: S2211-1247(20)30260-6. doi:, 10.1016/j.celrep.2020.02.086. PMID:32126208 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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