Heterodimeric structure of superoxide dismutase in complex with its metallochaperone

Audrey L. Lamb; Andrew S. Torres; Thomas V. O'Halloran; Amy C. Rosenzweig

doi:10.1038/nsb0901-751

Heterodimeric structure of superoxide dismutase in complex with its metallochaperone

Audrey L. Lamb, Andrew S. Torres, Thomas V. O'Halloran, Amy C. Rosenzweig^*

^*Corresponding author for this work

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

249 Scopus citations

Abstract

The copper chaperone for superoxide dismutase (CCS) activates the eukaryotic antioxidant enzyme copper, zinc superoxide dismutase (SOD1). The 2.9 Å resolution structure of yeast SOD1 complexed with yeast CCS (yCCS) reveals that SOD1 interacts with its metallochaperone to form a complex comprising one monomer of each protein. The heterodimer interface is remarkably similar to the SOD1 and yCCS homodimer interfaces. Striking conformational rearrangements are observed in both the chaperone and target enzyme upon complex formation, and the functionally essential C-terminal domain of yCCS is well positioned to play a key role in the metal ion transfer mechanism. This domain is linked to SOD1 by an intermolecular disulfide bond that may facilitate or regulate copper delivery.

Original language	English (US)
Pages (from-to)	751-755
Number of pages	5
Journal	Nature Structural Biology
Volume	8
Issue number	9
DOIs	https://doi.org/10.1038/nsb0901-751
State	Published - 2001

ASJC Scopus subject areas

Structural Biology
Biochemistry
Genetics

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@article{73bdd2f574c14c11801663519cfba9d9,

title = "Heterodimeric structure of superoxide dismutase in complex with its metallochaperone",

abstract = "The copper chaperone for superoxide dismutase (CCS) activates the eukaryotic antioxidant enzyme copper, zinc superoxide dismutase (SOD1). The 2.9 {\AA} resolution structure of yeast SOD1 complexed with yeast CCS (yCCS) reveals that SOD1 interacts with its metallochaperone to form a complex comprising one monomer of each protein. The heterodimer interface is remarkably similar to the SOD1 and yCCS homodimer interfaces. Striking conformational rearrangements are observed in both the chaperone and target enzyme upon complex formation, and the functionally essential C-terminal domain of yCCS is well positioned to play a key role in the metal ion transfer mechanism. This domain is linked to SOD1 by an intermolecular disulfide bond that may facilitate or regulate copper delivery.",

author = "Lamb, {Audrey L.} and Torres, {Andrew S.} and O'Halloran, {Thomas V.} and Rosenzweig, {Amy C.}",

note = "Funding Information: This work was supported by an NIH grant to A.C.R., by a grant from the ALS Association to A.C.R. and by an NIH NRSA Fellowship to A.L.L. The DND-CAT Synchrotron Research Center at the Advanced Photon Source is supported by the E.I. DuPont de Nemours & Co., the Dow Chemical Co., the State of Illinois, the U. S. Department of Energy and the NSF.",

year = "2001",

doi = "10.1038/nsb0901-751",

language = "English (US)",

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pages = "751--755",

journal = "Nature Structural Biology",

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T1 - Heterodimeric structure of superoxide dismutase in complex with its metallochaperone

AU - Lamb, Audrey L.

AU - Torres, Andrew S.

AU - O'Halloran, Thomas V.

AU - Rosenzweig, Amy C.

N1 - Funding Information: This work was supported by an NIH grant to A.C.R., by a grant from the ALS Association to A.C.R. and by an NIH NRSA Fellowship to A.L.L. The DND-CAT Synchrotron Research Center at the Advanced Photon Source is supported by the E.I. DuPont de Nemours & Co., the Dow Chemical Co., the State of Illinois, the U. S. Department of Energy and the NSF.

PY - 2001

Y1 - 2001

N2 - The copper chaperone for superoxide dismutase (CCS) activates the eukaryotic antioxidant enzyme copper, zinc superoxide dismutase (SOD1). The 2.9 Å resolution structure of yeast SOD1 complexed with yeast CCS (yCCS) reveals that SOD1 interacts with its metallochaperone to form a complex comprising one monomer of each protein. The heterodimer interface is remarkably similar to the SOD1 and yCCS homodimer interfaces. Striking conformational rearrangements are observed in both the chaperone and target enzyme upon complex formation, and the functionally essential C-terminal domain of yCCS is well positioned to play a key role in the metal ion transfer mechanism. This domain is linked to SOD1 by an intermolecular disulfide bond that may facilitate or regulate copper delivery.

AB - The copper chaperone for superoxide dismutase (CCS) activates the eukaryotic antioxidant enzyme copper, zinc superoxide dismutase (SOD1). The 2.9 Å resolution structure of yeast SOD1 complexed with yeast CCS (yCCS) reveals that SOD1 interacts with its metallochaperone to form a complex comprising one monomer of each protein. The heterodimer interface is remarkably similar to the SOD1 and yCCS homodimer interfaces. Striking conformational rearrangements are observed in both the chaperone and target enzyme upon complex formation, and the functionally essential C-terminal domain of yCCS is well positioned to play a key role in the metal ion transfer mechanism. This domain is linked to SOD1 by an intermolecular disulfide bond that may facilitate or regulate copper delivery.

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JO - Nature Structural Biology

JF - Nature Structural Biology

IS - 9

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Heterodimeric structure of superoxide dismutase in complex with its metallochaperone

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