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| <StructureSection load='6n85' size='340' side='right'caption='[[6n85]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='6n85' size='340' side='right'caption='[[6n85]], [[Resolution|resolution]] 2.50Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6n85]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N85 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n85]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N85 FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RIC8A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN]), GNAT2, GNATC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene></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=6n85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n85 OCA], [https://pdbe.org/6n85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n85 RCSB], [https://www.ebi.ac.uk/pdbsum/6n85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n85 ProSAT]</span></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=6n85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n85 OCA], [https://pdbe.org/6n85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n85 RCSB], [https://www.ebi.ac.uk/pdbsum/6n85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n85 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[https://www.uniprot.org/uniprot/RIC8A_BOVIN RIC8A_BOVIN]] 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 (By similarity). [[https://www.uniprot.org/uniprot/MALE_ECO57 MALE_ECO57]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides (By similarity).
| + | [https://www.uniprot.org/uniprot/RIC8A_BOVIN RIC8A_BOVIN] 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 (By similarity). |
| <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: Bovin]] | + | [[Category: Bos taurus]] |
- | [[Category: Human]] | + | [[Category: Escherichia coli O157:H7]] |
| + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Artemyev, N O]] | + | [[Category: Artemyev NO]] |
- | [[Category: Gakhar, L]] | + | [[Category: Gakhar L]] |
- | [[Category: Srivastava, D]] | + | [[Category: Srivastava D]] |
- | [[Category: Armadillo repeat]]
| + | |
- | [[Category: Chaperone]]
| + | |
- | [[Category: G alpha]]
| + | |
- | [[Category: Mbp]]
| + | |
- | [[Category: Ric8a]]
| + | |
| Structural highlights
Function
RIC8A_BOVIN 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 (By similarity).
Publication Abstract from PubMed
Resistance to inhibitors of cholinesterase 8A (Ric8A) is an essential regulator of G protein alpha-subunits (Galpha), acting as a guanine nucleotide exchange factor and a chaperone. We report two crystal structures of Ric8A, one in the apo form and the other in complex with a tagged C-terminal fragment of Galpha. These structures reveal two principal domains of Ric8A: an armadillo-fold core and a flexible C-terminal tail. Additionally, they show that the Galpha C-terminus binds to a highly-conserved patch on the concave surface of the Ric8A armadillo-domain, with selectivity determinants residing in the Galpha sequence. Biochemical analysis shows that the Ric8A C-terminal tail is critical for its stability and function. A model of the Ric8A/Galpha complex derived from crosslinking mass spectrometry and molecular dynamics simulations suggests that the Ric8A C-terminal tail helps organize the GTP-binding site of Galpha. This study lays the groundwork for understanding Ric8A function at the molecular level.
Structural underpinnings of Ric8A function as a G-protein alpha-subunit chaperone and guanine-nucleotide exchange factor.,Srivastava D, Gakhar L, Artemyev NO Nat Commun. 2019 Jul 12;10(1):3084. doi: 10.1038/s41467-019-11088-x. PMID:31300652[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Srivastava D, Gakhar L, Artemyev NO. Structural underpinnings of Ric8A function as a G-protein alpha-subunit chaperone and guanine-nucleotide exchange factor. Nat Commun. 2019 Jul 12;10(1):3084. doi: 10.1038/s41467-019-11088-x. PMID:31300652 doi:http://dx.doi.org/10.1038/s41467-019-11088-x
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