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| | ==Solution structure of bb' domains of human protein disulfide isomerase== | | ==Solution structure of bb' domains of human protein disulfide isomerase== |
| - | <StructureSection load='2k18' size='340' side='right'caption='[[2k18]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2k18' size='340' side='right'caption='[[2k18]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2k18]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K18 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k18]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K18 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bjx|1bjx]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">P4HB, ERBA2L, PDI, PDIA1, PO4DB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein_disulfide-isomerase Protein disulfide-isomerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.4.1 5.3.4.1] </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=2k18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k18 OCA], [https://pdbe.org/2k18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k18 RCSB], [https://www.ebi.ac.uk/pdbsum/2k18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k18 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=2k18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k18 OCA], [https://pdbe.org/2k18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k18 RCSB], [https://www.ebi.ac.uk/pdbsum/2k18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k18 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein disulfide-isomerase]]
| + | [[Category: Dabrowski C]] |
| - | [[Category: Dabrowski, C]] | + | [[Category: Denisov AY]] |
| - | [[Category: Denisov, A Y]] | + | [[Category: Gehring K]] |
| - | [[Category: Gehring, K]] | + | [[Category: Kozlov G]] |
| - | [[Category: Kozlov, G]] | + | [[Category: Maattanen P]] |
| - | [[Category: Maattanen, P]] | + | [[Category: Thomas DY]] |
| - | [[Category: Thomas, D Y]] | + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Pdi]]
| + | |
| - | [[Category: Protein folding]]
| + | |
| - | [[Category: Redox-active center]]
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Protein disulfide isomerase is the most abundant and best studied of the disulfide isomerases that catalyze disulfide bond formation in the endoplasmic reticulum, yet the specifics of how it binds substrate have been elusive. Protein disulfide isomerase is composed of four thioredoxin-like domains (abb'a'). Cross-linking studies with radiolabeled peptides and unfolded proteins have shown that it binds incompletely folded proteins primarily via its third domain, b'. Here, we determined the solution structure of the second and third domains of human protein disulfide isomerase (b and b', respectively) by triple-resonance NMR spectroscopy and molecular modeling. NMR titrations identified a large hydrophobic surface within the b' domain that binds unfolded ribonuclease A and the peptides mastoparan and somatostatin. Protein disulfide isomerase-catalyzed refolding of reduced ribonuclease A in vitro was inhibited by these peptides at concentrations equal to their affinity to the bb' fragment. Our findings provide a structural basis for previous kinetic and cross-linking studies which have shown that protein disulfide isomerase exhibits a saturable, substrate-binding site.
Solution structure of the bb' domains of human protein disulfide isomerase.,Denisov AY, Maattanen P, Dabrowski C, Kozlov G, Thomas DY, Gehring K FEBS J. 2009 Mar;276(5):1440-9. PMID:19187238[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
- ↑ Denisov AY, Maattanen P, Dabrowski C, Kozlov G, Thomas DY, Gehring K. Solution structure of the bb' domains of human protein disulfide isomerase. FEBS J. 2009 Mar;276(5):1440-9. PMID:19187238 doi:EJB6884
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