7d72
From Proteopedia
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| - | ==== | + | ==Cryo-EM structures of human GMPPA/GMPPB complex bound to GDP-Mannose== |
| - | <StructureSection load='7d72' size='340' side='right'caption='[[7d72]]' scene=''> | + | <StructureSection load='7d72' size='340' side='right'caption='[[7d72]], [[Resolution|resolution]] 3.40Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7d72]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D72 FirstGlance]. <br> |
| - | </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=7d72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d72 OCA], [https://pdbe.org/7d72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d72 RCSB], [https://www.ebi.ac.uk/pdbsum/7d72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d72 ProSAT]</span></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]] 3.4Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDD:GUANOSINE-5-DIPHOSPHATE-ALPHA-D-MANNOSE'>GDD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7d72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d72 OCA], [https://pdbe.org/7d72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d72 RCSB], [https://www.ebi.ac.uk/pdbsum/7d72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d72 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/GMPPA_HUMAN GMPPA_HUMAN] Triple A syndrome. The disease is caused by variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GMPPA_HUMAN GMPPA_HUMAN] Regulatory subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex; reduces the catalytic activity of GMPPB when part of the complex (PubMed:24035193, PubMed:33986552). Mediates allosteric feedback inhibition of GMPPB catalytic activity upon binding GDP-alpha-D-mannose (PubMed:24035193, PubMed:33986552). Together with GMPPB regulates GDP-alpha-D-mannose levels (PubMed:33986552).<ref>PMID:24035193</ref> <ref>PMID:33986552</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | GDP-mannose (GDP-Man) is a key metabolite essential for protein glycosylation and glycophosphatidylinositol anchor synthesis, and aberrant cellular GDP-Man levels have been associated with multiple human diseases. How cells maintain homeostasis of GDP-Man is unknown. Here, we report the cryo-EM structures of human GMPPA-GMPPB complex, the protein machinery responsible for GDP-Man synthesis, in complex with GDP-Man or GTP. Unexpectedly, we find that the catalytically inactive subunit GMPPA displays a much higher affinity to GDP-Man than the active subunit GMPPB and, subsequently, inhibits the catalytic activity of GMPPB through a unique C-terminal loop of GMPPA. Importantly, disruption of the interactions between GMPPA and GMPPB or the binding of GDP-Man to GMPPA in zebrafish leads to abnormal brain development and muscle abnormality, analogous to phenotypes observed in individuals carrying GMPPA or GMPPB mutations. We conclude that GMPPA acts as a cellular sensor to maintain mannose homeostasis through allosterically regulating GMPPB. | ||
| + | |||
| + | Cryo-EM structures of human GMPPA-GMPPB complex reveal how cells maintain GDP-mannose homeostasis.,Zheng L, Liu Z, Wang Y, Yang F, Wang J, Huang W, Qin J, Tian M, Cai X, Liu X, Mo X, Gao N, Jia D Nat Struct Mol Biol. 2021 May;28(5):1-12. doi: 10.1038/s41594-021-00591-9. Epub , 2021 May 13. PMID:33986552<ref>PMID:33986552</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7d72" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Z | + | [[Category: Cai X]] |
| + | [[Category: Gao N]] | ||
| + | [[Category: Jia D]] | ||
| + | [[Category: Liu Z]] | ||
| + | [[Category: Mo X]] | ||
| + | [[Category: Qing J]] | ||
| + | [[Category: Wang J]] | ||
| + | [[Category: Wang Y]] | ||
| + | [[Category: Yang F]] | ||
| + | [[Category: Zheng L]] | ||
Current revision
Cryo-EM structures of human GMPPA/GMPPB complex bound to GDP-Mannose
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Categories: Homo sapiens | Large Structures | Cai X | Gao N | Jia D | Liu Z | Mo X | Qing J | Wang J | Wang Y | Yang F | Zheng L
