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| | <StructureSection load='5gu7' size='340' side='right'caption='[[5gu7]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='5gu7' size='340' side='right'caption='[[5gu7]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5gu7]] is a 1 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=5GU7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5GU7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5gu7]] is a 1 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=5GU7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GU7 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5gu6|5gu6]]</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]] 2.05Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5gu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gu7 OCA], [https://pdbe.org/5gu7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gu7 RCSB], [https://www.ebi.ac.uk/pdbsum/5gu7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gu7 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5gu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gu7 OCA], [http://pdbe.org/5gu7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gu7 RCSB], [http://www.ebi.ac.uk/pdbsum/5gu7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gu7 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5gu7" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5gu7" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[ER-resident protein|ER-resident protein]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Inaba, K]] | + | [[Category: Inaba K]] |
| - | [[Category: Watanabe, S]] | + | [[Category: Watanabe S]] |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Quality control]]
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| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
ERp44 retrieves some endoplasmic reticulum (ER)-resident enzymes and immature oligomers of secretory proteins from the Golgi. Association of ERp44 with its clients is regulated by pH-dependent mechanisms, but the molecular details are not fully understood. Here we report high-resolution crystal structures of human ERp44 at neutral and weakly acidic pH. These structures reveal key regions in the C-terminal tail (C tail) missing in the original crystal structure, including a regulatory histidine-rich region and a subsequent extended loop. The former region forms a short alpha-helix (alpha16), generating a histidine-clustered site (His cluster). At low pH, the three Trx-like domains of ERp44 ("a," "b," and "b'") undergo significant rearrangements, likely induced by protonation of His157 located at the interface between the a and b domains. The alpha16-helix is partially unwound and the extended loop is disordered in weakly acidic conditions, probably due to electrostatic repulsion between the protonated histidines in the His cluster. Molecular dynamics simulations indicated that helix unwinding enhances the flexibility of the C tail, disrupting its normal hydrogen-bonding pattern. The observed pH-dependent conformational changes significantly enlarge the positively charged regions around the client-binding site of ERp44 at low pH. Mutational analyses showed that ERp44 forms mixed disulfides with specific cysteines residing on negatively charged loop regions of Ero1alpha. We propose that the protonation states of the essential histidines regulate the ERp44-client interaction by altering the C-tail dynamics and surface electrostatic potential of ERp44.
Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface.,Watanabe S, Harayama M, Kanemura S, Sitia R, Inaba K Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3224-E3232. doi:, 10.1073/pnas.1621426114. Epub 2017 Apr 3. PMID:28373561[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Anelli T, Alessio M, Mezghrani A, Simmen T, Talamo F, Bachi A, Sitia R. ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J. 2002 Feb 15;21(4):835-44. PMID:11847130 doi:http://dx.doi.org/10.1093/emboj/21.4.835
- ↑ Anelli T, Alessio M, Bachi A, Bergamelli L, Bertoli G, Camerini S, Mezghrani A, Ruffato E, Simmen T, Sitia R. Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO J. 2003 Oct 1;22(19):5015-22. PMID:14517240 doi:http://dx.doi.org/10.1093/emboj/cdg491
- ↑ Watanabe S, Harayama M, Kanemura S, Sitia R, Inaba K. Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface. Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3224-E3232. doi:, 10.1073/pnas.1621426114. Epub 2017 Apr 3. PMID:28373561 doi:http://dx.doi.org/10.1073/pnas.1621426114
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