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3uem

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Revision as of 18:05, 25 December 2014

Crystal structure of human PDI bb'a' domains

Structural highlights

3uem is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	PDI (Homo sapiens)
Activity:	Protein disulfide-isomerase, with EC number 5.3.4.1
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

Protein-disulfide isomerase (PDI), with domains arranged as abb'xa'c, is a key enzyme and chaperone localized in the endoplasmic reticulum (ER) catalyzing oxidative folding and preventing misfolding/aggregation of proteins. It has been controversial whether the chaperone activity of PDI is redox-regulated, and the molecular basis is unclear. Here, we show that both the chaperone activity and the overall conformation of human PDI are redox-regulated. We further demonstrate that the conformational changes are triggered by the active site of domain a', and the minimum redox-regulated cassette is located in b'xa'. The structure of the reduced bb'xa' reveals for the first time that domain a' packs tightly with both domain b' and linker x to form one compact structural module. Oxidation of domain a' releases the compact conformation and exposes the shielded hydrophobic areas to facilitate its high chaperone activity. Thus, the study unequivocally provides mechanistic insights into the redox-regulated chaperone activity of human PDI.

Human protein-disulfide isomerase is a redox-regulated chaperone activated by oxidation of domain a'.,Wang C, Yu J, Huo L, Wang L, Feng W, Wang CC J Biol Chem. 2012 Jan 6;287(2):1139-49. Epub 2011 Nov 16. PMID:22090031^[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, Yu J, Huo L, Wang L, Feng W, Wang CC. Human protein-disulfide isomerase is a redox-regulated chaperone activated by oxidation of domain a'. J Biol Chem. 2012 Jan 6;287(2):1139-49. Epub 2011 Nov 16. PMID:22090031 doi:10.1074/jbc.M111.303149

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3uem"

@@ Line 8: / Line 8: @@
 <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=3uem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uem OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uem RCSB], [http://www.ebi.ac.uk/pdbsum/3uem PDBsum]</span></td></tr>
 </table>
+== 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

3uem

From Proteopedia

Revision as of 18:05, 25 December 2014

Crystal structure of human PDI bb'a' domains

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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