Document Detail

Molecular bases of cyclic and specific disulfide interchange between human ERO1alpha protein and protein-disulfide isomerase (PDI).
MedLine Citation:
PMID:  21398518     Owner:  NLM     Status:  MEDLINE    
In the endoplasmic reticulum (ER) of human cells, ERO1α and protein-disulfide isomerase (PDI) constitute one of the major electron flow pathways that catalyze oxidative folding of secretory proteins. Specific and limited PDI oxidation by ERO1α is essential to avoid ER hyperoxidation. To investigate how ERO1α oxidizes PDI selectively among more than 20 ER-resident PDI family member proteins, we performed docking simulations and systematic biochemical analyses. Our findings reveal that a protruding β-hairpin of ERO1α specifically interacts with the hydrophobic pocket present in the redox-inactive PDI b'-domain through the stacks between their aromatic residues, leading to preferred oxidation of the C-terminal PDI a'-domain. ERO1α associated preferentially with reduced PDI, explaining the stepwise disulfide shuttle mechanism, first from ERO1α to PDI and then from oxidized PDI to an unfolded polypeptide bound to its hydrophobic pocket. The interaction of ERO1α with ERp44, another PDI family member protein, was also analyzed. Notably, ERO1α-dependent PDI oxidation was inhibited by a hyperactive ERp44 mutant that lacks the C-terminal tail concealing the substrate-binding hydrophobic regions. The potential ability of ERp44 to inhibit ERO1α activity may suggest its physiological role in ER redox and protein homeostasis.
Shoji Masui; Stefano Vavassori; Claudio Fagioli; Roberto Sitia; Kenji Inaba
Related Documents :
21404418 - Coupling proteomics and transcriptomics for the identification of novel and variant for...
23399118 - Characterization and controlled release aloe extract of collagen protein modified cotto...
8789148 - Membrane protein subunit fractionation by means of inverse pore gradient elution polyac...
6842088 - Quantitation of hepatic fatty acid-binding proteins by post-chromatographic ligand bind...
2143168 - Immunohistochemical localization of a plasma protein (glycoprotein 60) which inhibits c...
9130078 - A new spatial representation of amino acid residues in globular proteins.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-11
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-07-01     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16261-71     Citation Subset:  IM    
Division of Protein Chemistry, Post-Genome Science Center, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Binding Sites
Disulfides / chemistry*,  metabolism
Membrane Glycoproteins / chemistry*,  genetics,  metabolism
Membrane Proteins / chemistry,  genetics,  metabolism
Molecular Chaperones / chemistry,  genetics,  metabolism
Oxidoreductases / chemistry*,  genetics,  metabolism
Protein Disulfide-Isomerases / chemistry*,  genetics,  metabolism
Protein Folding*
Protein Structure, Secondary
Reg. No./Substance:
0/Disulfides; 0/ERP44 protein, human; 0/Membrane Glycoproteins; 0/Membrane Proteins; 0/Molecular Chaperones; EC 1.-/ERO1L protein, human; EC 1.-/Oxidoreductases; EC Disulfide-Isomerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Relocalizing genetic loci into specific subnuclear neighborhoods.
Next Document:  Difference in stability of the N-domain underlies distinct intracellular properties of the E1064A an...