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| | <StructureSection load='5xwm' size='340' side='right'caption='[[5xwm]], [[Resolution|resolution]] 2.45Å' scene=''> | | <StructureSection load='5xwm' size='340' side='right'caption='[[5xwm]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xwm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XWM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XWM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xwm]] is a 4 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=5XWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XWM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.45Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERP44, KIAA0573, TXNDC4, UNQ532/PRO1075 ([http://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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5xwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xwm OCA], [http://pdbe.org/5xwm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xwm RCSB], [http://www.ebi.ac.uk/pdbsum/5xwm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xwm 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=5xwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xwm OCA], [https://pdbe.org/5xwm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xwm RCSB], [https://www.ebi.ac.uk/pdbsum/5xwm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xwm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ERP44_HUMAN ERP44_HUMAN]] Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif. Inhibits the calcium channel activity of ITPR1. May have a role in the control of oxidative protein folding in the endoplasmic reticulum. Required to retain ERO1L and ERO1LB in the endoplasmic reticulum.<ref>PMID:11847130</ref> <ref>PMID:14517240</ref> | + | [https://www.uniprot.org/uniprot/ERP44_HUMAN ERP44_HUMAN] Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif. Inhibits the calcium channel activity of ITPR1. May have a role in the control of oxidative protein folding in the endoplasmic reticulum. Required to retain ERO1L and ERO1LB in the endoplasmic reticulum.<ref>PMID:11847130</ref> <ref>PMID:14517240</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Zinc ions (Zn(2+)) are imported into the early secretory pathway by Golgi-resident transporters, but their handling and functions are not fully understood. Here, we show that Zn(2+) binds with high affinity to the pH-sensitive chaperone ERp44, modulating its localization and ability to retrieve clients like Ero1alpha and ERAP1 to the endoplasmic reticulum (ER). Silencing the Zn(2+) transporters that uptake Zn(2+) into the Golgi led to ERp44 dysfunction and increased secretion of Ero1alpha and ERAP1. High-resolution crystal structures of Zn(2+)-bound ERp44 reveal that Zn(2+) binds to a conserved histidine-cluster. The consequent large displacements of the regulatory C-terminal tail expose the substrate-binding surface and RDEL motif, ensuring client capture and retrieval. ERp44 also forms Zn(2+)-bridged homodimers, which dissociate upon client binding. Histidine mutations in the Zn(2+)-binding sites compromise ERp44 activity and localization. Our findings reveal a role of Zn(2+) as a key regulator of protein quality control at the ER-Golgi interface.
| + | |
| - | | + | |
| - | Zinc regulates ERp44-dependent protein quality control in the early secretory pathway.,Watanabe S, Amagai Y, Sannino S, Tempio T, Anelli T, Harayama M, Masui S, Sorrentino I, Yamada M, Sitia R, Inaba K Nat Commun. 2019 Feb 5;10(1):603. doi: 10.1038/s41467-019-08429-1. PMID:30723194<ref>PMID:30723194</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5xwm" style="background-color:#fffaf0;"></div>
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| - | | + | |
| - | ==See Also==
| + | |
| - | *[[ER-resident protein|ER-resident protein]]
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Harayama, M]] | + | [[Category: Harayama M]] |
| - | [[Category: Inaba, K]] | + | [[Category: Inaba K]] |
| - | [[Category: Watanabe, S]] | + | [[Category: Watanabe S]] |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
