Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site

Morgan M. Fetherolf, Stefanie D. Boyd, Alexander B. Taylor, Hee Jong Kim, James A. Wohlschlegel, Ninian Blackburn, P. John Hart, Dennis R. Winge, Duane D. Winkler

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Metallochaperones are a diverse family of trafficking molecules that provide metal ions to protein targets for use as cofactors. The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond. Here, we present structural, spectroscopic, and cell-based data supporting a novel copper-induced mechanism for Sod1 activation. Ccs1 binding exposes an electropositive cavity and proposed “entry site” for copper ion delivery on immature Sod1. Copper-mediated sulfenylation leads to a sulfenic acid intermediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper into the Sod1 active site. Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment.

Original languageEnglish (US)
Pages (from-to)12025-12040
Number of pages16
JournalJournal of Biological Chemistry
Volume292
Issue number29
DOIs
StatePublished - 2017

Fingerprint

Sulfenic Acids
Superoxide Dismutase
Zinc
Copper
Ions
Disulfides
Metallochaperones
Protein Disulfide Reductase (Glutathione)
Metal ions
Catalytic Domain
Cytoplasm
Metals
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fetherolf, M. M., Boyd, S. D., Taylor, A. B., Kim, H. J., Wohlschlegel, J. A., Blackburn, N., ... Winkler, D. D. (2017). Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site. Journal of Biological Chemistry, 292(29), 12025-12040. https://doi.org/10.1074/jbc.M117.775981

Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site. / Fetherolf, Morgan M.; Boyd, Stefanie D.; Taylor, Alexander B.; Kim, Hee Jong; Wohlschlegel, James A.; Blackburn, Ninian; Hart, P. John; Winge, Dennis R.; Winkler, Duane D.

In: Journal of Biological Chemistry, Vol. 292, No. 29, 2017, p. 12025-12040.

Research output: Contribution to journalArticle

Fetherolf, MM, Boyd, SD, Taylor, AB, Kim, HJ, Wohlschlegel, JA, Blackburn, N, Hart, PJ, Winge, DR & Winkler, DD 2017, 'Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site', Journal of Biological Chemistry, vol. 292, no. 29, pp. 12025-12040. https://doi.org/10.1074/jbc.M117.775981
Fetherolf, Morgan M. ; Boyd, Stefanie D. ; Taylor, Alexander B. ; Kim, Hee Jong ; Wohlschlegel, James A. ; Blackburn, Ninian ; Hart, P. John ; Winge, Dennis R. ; Winkler, Duane D. / Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 29. pp. 12025-12040.
@article{69b8a043ff7846b3ba794c988ee360c4,
title = "Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site",
abstract = "Metallochaperones are a diverse family of trafficking molecules that provide metal ions to protein targets for use as cofactors. The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond. Here, we present structural, spectroscopic, and cell-based data supporting a novel copper-induced mechanism for Sod1 activation. Ccs1 binding exposes an electropositive cavity and proposed “entry site” for copper ion delivery on immature Sod1. Copper-mediated sulfenylation leads to a sulfenic acid intermediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper into the Sod1 active site. Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment.",
author = "Fetherolf, {Morgan M.} and Boyd, {Stefanie D.} and Taylor, {Alexander B.} and Kim, {Hee Jong} and Wohlschlegel, {James A.} and Ninian Blackburn and Hart, {P. John} and Winge, {Dennis R.} and Winkler, {Duane D.}",
year = "2017",
doi = "10.1074/jbc.M117.775981",
language = "English (US)",
volume = "292",
pages = "12025--12040",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "29",

}

TY - JOUR

T1 - Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site

AU - Fetherolf, Morgan M.

AU - Boyd, Stefanie D.

AU - Taylor, Alexander B.

AU - Kim, Hee Jong

AU - Wohlschlegel, James A.

AU - Blackburn, Ninian

AU - Hart, P. John

AU - Winge, Dennis R.

AU - Winkler, Duane D.

PY - 2017

Y1 - 2017

N2 - Metallochaperones are a diverse family of trafficking molecules that provide metal ions to protein targets for use as cofactors. The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond. Here, we present structural, spectroscopic, and cell-based data supporting a novel copper-induced mechanism for Sod1 activation. Ccs1 binding exposes an electropositive cavity and proposed “entry site” for copper ion delivery on immature Sod1. Copper-mediated sulfenylation leads to a sulfenic acid intermediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper into the Sod1 active site. Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment.

AB - Metallochaperones are a diverse family of trafficking molecules that provide metal ions to protein targets for use as cofactors. The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond. Here, we present structural, spectroscopic, and cell-based data supporting a novel copper-induced mechanism for Sod1 activation. Ccs1 binding exposes an electropositive cavity and proposed “entry site” for copper ion delivery on immature Sod1. Copper-mediated sulfenylation leads to a sulfenic acid intermediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper into the Sod1 active site. Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment.

UR - http://www.scopus.com/inward/record.url?scp=85025175819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85025175819&partnerID=8YFLogxK

U2 - 10.1074/jbc.M117.775981

DO - 10.1074/jbc.M117.775981

M3 - Article

VL - 292

SP - 12025

EP - 12040

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 29

ER -