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| | <StructureSection load='6vu8' size='340' side='right'caption='[[6vu8]], [[Resolution|resolution]] 4.14Å' scene=''> | | <StructureSection load='6vu8' size='340' side='right'caption='[[6vu8]], [[Resolution|resolution]] 4.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vu8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VU8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6VU8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vu8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VU8 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.14Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6vu5|6vu5]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ric8a, rCG_48458 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), GNAI1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6vu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vu8 OCA], [https://pdbe.org/6vu8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vu8 RCSB], [https://www.ebi.ac.uk/pdbsum/6vu8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vu8 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6vu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vu8 OCA], [http://pdbe.org/6vu8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vu8 RCSB], [http://www.ebi.ac.uk/pdbsum/6vu8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vu8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GNAI1_HUMAN 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.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref> | + | [https://www.uniprot.org/uniprot/RIC8A_RAT 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.<ref>PMID:12509430</ref> <ref>PMID:16275912</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hilger, D]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Seven, A B]] | + | [[Category: Hilger D]] |
| - | [[Category: Chaperone]] | + | [[Category: Seven AB]] |
| - | [[Category: Cryoem structure]]
| + | |
| - | [[Category: G alpha folding]]
| + | |
| - | [[Category: G protein alpha subunit]]
| + | |
| - | [[Category: Molecular chaperone]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Protein complex]]
| + | |
| - | [[Category: Quality control]]
| + | |
| - | [[Category: Ric-8]]
| + | |
| Structural highlights
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.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tall GG, Krumins AM, Gilman AG. Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor. J Biol Chem. 2003 Mar 7;278(10):8356-62. PMID:12509430 doi:10.1074/jbc.M211862200
- ↑ Tall GG, Gilman AG. Resistance to inhibitors of cholinesterase 8A catalyzes release of Galphai-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Galphai-GDP complexes. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16584-9. PMID:16275912 doi:10.1073/pnas.0508306102
- ↑ Seven AB, Hilger D, Papasergi-Scott MM, Zhang L, Qu Q, Kobilka BK, Tall GG, Skiniotis G. Structures of Galpha Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms. Cell Rep. 2020 Feb 28. pii: S2211-1247(20)30260-6. doi:, 10.1016/j.celrep.2020.02.086. PMID:32126208 doi:http://dx.doi.org/10.1016/j.celrep.2020.02.086
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