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| | ==Crystal structure of oxidized hPDI (abb'xa')== | | ==Crystal structure of oxidized hPDI (abb'xa')== |
| - | <StructureSection load='4el1' size='340' side='right' caption='[[4el1]], [[Resolution|resolution]] 2.88Å' scene=''> | + | <StructureSection load='4el1' size='340' side='right'caption='[[4el1]], [[Resolution|resolution]] 2.88Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4el1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EL1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EL1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4el1]] is a 2 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=4EL1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EL1 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3uem|3uem]], [[4ekz|4ekz]]</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]] 2.883Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">P4HB, ERBA2L, PDI, PDIA1, PO4DB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4el1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4el1 OCA], [https://pdbe.org/4el1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4el1 RCSB], [https://www.ebi.ac.uk/pdbsum/4el1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4el1 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_disulfide-isomerase Protein disulfide-isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.4.1 5.3.4.1] </span></td></tr>
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| - | <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=4el1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4el1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4el1 RCSB], [http://www.ebi.ac.uk/pdbsum/4el1 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PDIA1_HUMAN PDIA1_HUMAN]] This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP.<ref>PMID:10636893</ref> <ref>PMID:12485997</ref> | + | [https://www.uniprot.org/uniprot/PDIA1_HUMAN PDIA1_HUMAN] This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP.<ref>PMID:10636893</ref> <ref>PMID:12485997</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4el1" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Protein disulfide-isomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Feng, W]] | + | [[Category: Feng W]] |
| - | [[Category: Gong, W]] | + | [[Category: Gong W]] |
| - | [[Category: Ke, H]] | + | [[Category: Ke H]] |
| - | [[Category: Li, W]] | + | [[Category: Li W]] |
| - | [[Category: Ren, J]] | + | [[Category: Ren J]] |
| - | [[Category: Wang, C]] | + | [[Category: Wang C]] |
| - | [[Category: Wang, C C]] | + | [[Category: Wang C-C]] |
| - | [[Category: Cghc active site]]
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| - | [[Category: A redox-regulated chaperone]]
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| - | [[Category: Abb'a' domain]]
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| - | [[Category: Chaperone]]
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| - | [[Category: Endoplasmic reticulum]]
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| - | [[Category: Enzyme]]
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| - | [[Category: Horseshoe shape]]
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| Structural highlights
Function
PDIA1_HUMAN This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP.[1] [2]
Publication Abstract from PubMed
Abstract Aim: Human protein disulfide isomerase (hPDI) is a key enzyme and a redox-regulated chaperone responsible for oxidative protein folding in the endoplasmic reticulum. This work aims to reveal the molecular mechanism underlying the redox-regulated functions of hPDI by determining the crystal structures of hPDI in different redox states. Results: The structures of hPDI (abb'xa') in both the reduced and oxidized states showed that the four thioredoxin domains of a, b, b', and a' are arranged as a horseshoe shape with two CGHC active sites, respectively, in domains a and a' facing each other at the two ends. In reduced hPDI, domains a, b, and b' line up in the same plane, whereas domain a' twists approximately 45 degrees out. The two active sites are 27.6 A apart. In oxidized hPDI, the four domains are differently organized to stay in the same plane, and the distance between the active sites increases to 40.3 A. In contrast to the closed conformation of reduced hPDI, oxidized hPDI exists in an open state with more exposed hydrophobic areas and a larger cleft with potential for substrate binding. Innovation: This is the first report of the high-resolution structures of hPDI containing all four domains in both the reduced and the oxidized states. It reveals the redox-regulated structural dynamic properties of the protein. Conclusion: The redox-regulated open/closed conformational switch of hPDI endows the protein with versatile target-binding capacities for its enzymatic and chaperone functions. Antioxid. Redox Signal. 00, 000-000.
Structural Insights into the Redox-Regulated Dynamic Conformations of Human Protein Disulfide Isomerase.,Wang C, Li W, Ren J, Fang J, Ke H, Gong W, Feng W, Wang CC Antioxid Redox Signal. 2012 Jul 9. PMID:22657537[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mezghrani A, Courageot J, Mani JC, Pugniere M, Bastiani P, Miquelis R. Protein-disulfide isomerase (PDI) in FRTL5 cells. pH-dependent thyroglobulin/PDI interactions determine a novel PDI function in the post-endoplasmic reticulum of thyrocytes. J Biol Chem. 2000 Jan 21;275(3):1920-9. PMID:10636893
- ↑ Lumb RA, Bulleid NJ. Is protein disulfide isomerase a redox-dependent molecular chaperone? EMBO J. 2002 Dec 16;21(24):6763-70. PMID:12485997
- ↑ Wang C, Li W, Ren J, Fang J, Ke H, Gong W, Feng W, Wang CC. Structural Insights into the Redox-Regulated Dynamic Conformations of Human Protein Disulfide Isomerase. Antioxid Redox Signal. 2012 Jul 9. PMID:22657537 doi:10.1089/ars.2012.4630
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