View source for 7d74


==Cryo-EM structure of GMPPA/GMPPB complex bound to GTP (state II)==
<StructureSection load='7d74' size='340' side='right'caption='[[7d74]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7d74]] 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=7D74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D74 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</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=7d74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d74 OCA], [https://pdbe.org/7d74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d74 RCSB], [https://www.ebi.ac.uk/pdbsum/7d74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d74 ProSAT]</span></td></tr>
</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7d74" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[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]]
[[Category: Cai X]]