Abstract
The CopC proteins are periplasmic copper binding proteins believed to play a role in bacterial copper homeostasis. Previous studies have focused on CopCs that are part of seven-protein Cop or Pco systems involved in copper resistance. These canonical CopCs contain distinct Cu(I) and Cu(II) binding sites. Mounting evidence suggests that CopCs are more widely distributed, often present only with the CopD inner membrane protein, frequently as a fusion protein, and that the CopC and CopD proteins together function in the uptake of copper to the cytoplasm. In the methanotroph Methylosinus trichosporium OB3b, genes encoding a CopCD pair are located adjacent to the particulate methane monooxygenase (pMMO) operon. The CopC from this organism (Mst-CopC) was expressed, purified, and structurally characterized. The 1.46 Å resolution crystal structure of Mst-CopC reveals a single Cu(II) binding site with coordination somewhat different from that in canonical CopCs, and the absence of a Cu(I) binding site. Extensive bioinformatic analyses indicate that the majority of CopCs in fact contain only a Cu(II) site, with just 10% of sequences corresponding to the canonical two-site CopC. Accordingly, a new classification scheme for CopCs was developed, and detailed analyses of the sequences and their genomic neighborhoods reveal new proteins potentially involved in copper homeostasis, providing a framework for expanded models of CopCD function.
Original language | English (US) |
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Pages (from-to) | 2278-2290 |
Number of pages | 13 |
Journal | Biochemistry |
Volume | 55 |
Issue number | 15 |
DOIs | |
State | Published - Apr 3 2016 |
Funding
Experiments performed at the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy Office of Science by Argonne National Laboratory, were supported by the U.S. Department of Energy under Contract DE-AC02-06CH11357. Use of LS-CAT Sector 21 was supported by the Michigan Economic Development Corp. and Michigan Technology Tri-Corridor Grant 085P1000817. GM/CA-CAT has been funded in whole or in part with Federal funds from National Institutes of Health Grant Y1-CO-1020 from the National Cancer Institute and Grant Y1-GM-1104 from the National Institute of General Medical Sciences. ICP-MS experiments were performed at the the Quantitative Bio-element Imaging Center at Northwestern University.
ASJC Scopus subject areas
- Biochemistry
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The crystal structure of CopC from Methylosinus trichosporium OB3b
Lawton, T. J. (Contributor), Kenney, G. E. (Contributor), Hurley, J. D. (Contributor) & Rosenzweig, A. C. (Contributor), Protein Data Bank (PDB), Apr 6 2016
DOI: 10.2210/pdb5ICU/pdb, https://www.wwpdb.org/pdb?id=pdb_00005icu
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