8k9q: Difference between revisions
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==Cryo-EM structure of the GPI inositol-deacylase (PGAP1/Bst1) from Chaetomium thermophilum== | |||
<StructureSection load='8k9q' size='340' side='right'caption='[[8k9q]], [[Resolution|resolution]] 2.84Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8k9q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum_var._thermophilum_DSM_1495 Chaetomium thermophilum var. thermophilum DSM 1495] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8K9Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8K9Q 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]] 2.84Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D39:(2~{S})-2-azanyl-3-[[(2~{R})-3-hexadecanoyloxy-2-[(~{Z})-octadec-9-enoyl]oxy-propoxy]-oxidanyl-phosphoryl]oxy-propanoic+acid'>D39</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=8k9q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8k9q OCA], [https://pdbe.org/8k9q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8k9q RCSB], [https://www.ebi.ac.uk/pdbsum/8k9q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8k9q ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/G0S652_CHATD G0S652_CHATD] Involved in inositol deacylation of GPI-anchored proteins which plays important roles in the quality control and ER-associated degradation of GPI-anchored proteins.[ARBA:ARBA00003496][RuleBase:RU365011] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The secretion and quality control of glycosylphosphatidylinositol-anchored proteins (GPI-APs) necessitates post-attachment remodeling initiated by the evolutionarily conserved PGAP1, which deacylates the inositol in nascent GPI-APs. Impairment of PGAP1 activity leads to developmental diseases in humans and fatality and infertility in animals. Here, we present three PGAP1 structures (2.66-2.84 A), revealing its 10-transmembrane architecture and product-enzyme interaction details. PGAP1 holds GPI-AP acyl chains in an optimally organized, guitar-shaped cavity with apparent energetic penalties from hydrophobic-hydrophilic mismatches. However, abundant glycan-mediated interactions in the lumen counterbalance these repulsions, likely conferring substrate fidelity and preventing off-target hydrolysis of bulk membrane lipids. Structural and biochemical analyses uncover a serine hydrolase-type catalysis with atypical features and imply mechanisms for substrate entrance and product release involving a drawing compass movement of GPI-APs. Our findings advance the mechanistic understanding of GPI-AP remodeling. | |||
Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis.,Hong J, Li T, Chao Y, Xu Y, Zhu Z, Zhou Z, Gu W, Qu Q, Li D Nat Commun. 2024 Jan 2;15(1):8. doi: 10.1038/s41467-023-44568-2. PMID:38167496<ref>PMID:38167496</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8k9q" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Chaetomium thermophilum var. thermophilum DSM 1495]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Hong J]] | |||
[[Category: Li D]] | |||
[[Category: Li T]] | |||
[[Category: Qu Q]] | |||
Latest revision as of 12:06, 30 October 2024
Cryo-EM structure of the GPI inositol-deacylase (PGAP1/Bst1) from Chaetomium thermophilum
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