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PMID: 10970843 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The CXXCXXC motif determines the folding, structure and stability of human Ero1-Lalpha.

The EMBO journal ·Vol. 19 ·No. 17 ·2000-09-01 ·Pages 4493-502

Benham AM, Cabibbo A, Fassio A, Bulleid N, Sitia R, Braakman I

Abstract

The presence of correctly formed disulfide bonds is crucial to the structure and function of proteins that are synthesized in the endoplasmic reticulum (ER). Disulfide bond formation occurs in the ER owing to the presence of several specialized catalysts and a suitable redox potential. Work in yeast has indicated that the ER resident glycoprotein Ero1p provides oxidizing equivalents to newly synthesized proteins via protein disulfide isomerase (PDI). Here we show that Ero1-Lalpha, the human homolog of Ero1p, exists as a collection of oxidized and reduced forms and covalently binds PDI. We analyzed Ero1-Lalpha cysteine mutants in the presumed active site C(391)VGCFKC(397). Our results demonstrate that this motif is important for protein folding, structural integrity, protein half-life and the stability of the Ero1-Lalpha-PDI complex.

MeSH Terms
Amino Acid Sequence Animals CHO Cells Cricetinae Disulfides/chemistry Endoplasmic Reticulum/chemistry Glycosylation HIV Envelope Protein gp120/chemistry HeLa Cells Humans Membrane Glycoproteins/chemistry Oxidation-Reduction Oxidoreductases Protein Conformation Protein Folding
Chemicals
Disulfides HIV Envelope Protein gp120 Membrane Glycoproteins ERO1A protein, human Oxidoreductases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Benham A M
Department of Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Cabibbo A
Fassio A
Bulleid N
Sitia R
Braakman I
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.17.4493
Published
2000-09-01
Pages
4493-502
Language
English
Region
England
NLM ID
8208664
PMCID
PMC302061
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.17.4493 PMC Full Text View journal details
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