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

A.M. Benham; A. Cabibbo; A. Fassio; N. Bulleid; R. Sitia; I. Braakman

doi:10.1093/emboj/19.17.4493

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

A.M. Benham, A. Cabibbo, A. Fassio, N. Bulleid, R. Sitia, I. Braakman

Research output: Contribution to journal › Article › Academic › peer-review

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-Lα, the human homolog of Ero1p, exists as a collection of oxidized and reduced forms and covalently binds PDI. We analyzed Ero1-Lα cysteine mutants in the presumed active site C391VGCFKC397. Our results demonstrate that this motif is important for protein folding, structural integrity, protein half-life and the stability of the Ero1-Lα-PDI complex.

Original language	English
Pages (from-to)	4493-4502
Number of pages	10
Journal	EMBO Journal
Volume	19
Issue number	17
DOIs	https://doi.org/10.1093/emboj/19.17.4493
Publication status	Published - 1 Sept 2000

Keywords

Chaperones
Disulfide bonds
Endoplasmic reticulum
Protein folding
Redox
article
catalyst
disulfide bond
endoplasmic reticulum
enzyme activity
oxidation reduction reaction
priority journal
protein folding
protein stability
protein structure
protein synthesis
structure activity relation

Access to Document

10.1093/emboj/19.17.4493

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC302061/

Cite this

@article{951fed2ec24942c89566b961dca48b74,

title = "The CXXCXXC motif determines the folding, structure and stability of human Ero1-Lα",

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-Lα, the human homolog of Ero1p, exists as a collection of oxidized and reduced forms and covalently binds PDI. We analyzed Ero1-Lα cysteine mutants in the presumed active site C391VGCFKC397. Our results demonstrate that this motif is important for protein folding, structural integrity, protein half-life and the stability of the Ero1-Lα-PDI complex.",

keywords = "Chaperones, Disulfide bonds, Endoplasmic reticulum, Protein folding, Redox, article, catalyst, disulfide bond, endoplasmic reticulum, enzyme activity, oxidation reduction reaction, priority journal, protein folding, protein stability, protein structure, protein synthesis, structure activity relation",

author = "A.M. Benham and A. Cabibbo and A. Fassio and N. Bulleid and R. Sitia and I. Braakman",

year = "2000",

month = sep,

day = "1",

doi = "10.1093/emboj/19.17.4493",

language = "English",

volume = "19",

pages = "4493--4502",

journal = "EMBO Journal",

issn = "0261-4189",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "17",

}

TY - JOUR

T1 - The CXXCXXC motif determines the folding, structure and stability of human Ero1-Lα

AU - Benham, A.M.

AU - Cabibbo, A.

AU - Fassio, A.

AU - Bulleid, N.

AU - Sitia, R.

AU - Braakman, I.

PY - 2000/9/1

Y1 - 2000/9/1

N2 - 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-Lα, the human homolog of Ero1p, exists as a collection of oxidized and reduced forms and covalently binds PDI. We analyzed Ero1-Lα cysteine mutants in the presumed active site C391VGCFKC397. Our results demonstrate that this motif is important for protein folding, structural integrity, protein half-life and the stability of the Ero1-Lα-PDI complex.

AB - 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-Lα, the human homolog of Ero1p, exists as a collection of oxidized and reduced forms and covalently binds PDI. We analyzed Ero1-Lα cysteine mutants in the presumed active site C391VGCFKC397. Our results demonstrate that this motif is important for protein folding, structural integrity, protein half-life and the stability of the Ero1-Lα-PDI complex.

KW - Chaperones

KW - Disulfide bonds

KW - Endoplasmic reticulum

KW - Protein folding

KW - Redox

KW - article

KW - catalyst

KW - disulfide bond

KW - endoplasmic reticulum

KW - enzyme activity

KW - oxidation reduction reaction

KW - priority journal

KW - protein folding

KW - protein stability

KW - protein structure

KW - protein synthesis

KW - structure activity relation

U2 - 10.1093/emboj/19.17.4493

DO - 10.1093/emboj/19.17.4493

M3 - Article

SN - 0261-4189

VL - 19

SP - 4493

EP - 4502

JO - EMBO Journal

JF - EMBO Journal

IS - 17

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this