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Crystal structure of the copper chaperone for superoxide dismutase

Nature Structural Biology volume 6, pages 724–729 (1999)Cite this article

Abstract

Cellular systems for handling transition metal ions have been identified, but little is known about the structure and function of the specific trafficking proteins. The 1.8 Å resolution structure of the yeast copper chaperone for superoxide dismutase (yCCS) reveals a protein composed of two domains. The N-terminal domain is very similar to the metallochaperone protein Atx1 and is likely to play a role in copper delivery and/or uptake. The second domain resembles the physiological target of yCCS, superoxide dismutase I (SOD1), in overall fold, but lacks all of the structural elements involved in catalysis. In the crystal, two SOD1-like domains interact to form a dimer. The subunit interface is remarkably similar to that in SOD1, suggesting a structural basis for target recognition by this metallochaperone.

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Figure 1: Structure of yCCS.
Figure 2: Comparison of the yCCS structure with Atx1 and SOD1.
Figure 3: Structure-based alignments comparing the amino acid sequences of CCS to Atx1 and to SOD1.
Figure 4: The dimerization interfaces of yCCS and ySOD1.

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Acknowledgements

We thank L. Pascoli and M. Hou for assistance with crystallization and J. Quintana and D. Keane for assistance with data collection. This work was supported by a grant from the NIH (to A.C.R.), by funds from the ALS Association (A.C.R.), by funds from the Robert H. Lurie Cancer Center (A.C.R.), by a grant from the NIH (to T.V.O.), by a supplement from NIGMS to this same grant (to A.C.R. and T.V.O.), by funds from the ALS Association (T.V.O.), and by an NIH NRSA Training Grant (R.A.P.). The DND-CAT Synchrotron Research Center at the Advanced Photon Sourceis supported by the E.I. Dupont de Nemours & Co., The Dow Chemical Company, the NSF and the State of Illinois.

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Authors and Affiliations

  1. Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, 60208, Illinois , USA

    Audrey L. Lamb, Amy K. Wernimont, Thomas V. O'Halloran & Amy C. Rosenzweig

  2. Department of Chemistry, Northwestern University, Evanston, 60208, Illinois, USA

    Audrey L. Lamb, Robert A. Pufahl, Thomas V. O'Halloran & Amy C. Rosenzweig

  3. Departments of Environmental Health Sciences and Biochemistry, Johns Hopkins University School of Public Health, Baltimore, 21205, Maryland, USA

    Valeria C. Culotta

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Correspondence to Amy C. Rosenzweig.

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Lamb, A., Wernimont, A., Pufahl, R. et al. Crystal structure of the copper chaperone for superoxide dismutase. Nat Struct Mol Biol 6, 724–729 (1999). https://doi.org/10.1038/11489

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