Abstract
Human CTR1 is a high-affinity copper transporter that also mediates the uptake of the anticancer drug cisplatin by largely unknown transport mechanisms. Here we report the 6-A projection structure obtained for human CTR1 by using electron crystallography of 2D protein crystals in a native phospholipid bilayer. The projection of CTR1 reveals a symmetrical trimer that is <40 A wide. Notably, the center threefold axis of each trimer forms a region of very low electron density likely to be involved in copper translocation. The formation of a putative pore for metal ions at the interface of three identical subunits deviates from the structural design of typical primary and secondary active transporters and reveals that copper uptake transporters have a novel architecture that is structurally more closely related to channel proteins.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / metabolism
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Biophysical Phenomena
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Biophysics
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Cation Transport Proteins / chemistry*
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism
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Cation Transport Proteins / ultrastructure
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Cisplatin / metabolism
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Copper / metabolism
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Copper Transporter 1
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Crystallography, X-Ray
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Genetic Complementation Test
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Humans
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Image Processing, Computer-Assisted
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In Vitro Techniques
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Microscopy, Electron
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Models, Molecular
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Mutagenesis
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Protein Structure, Quaternary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / ultrastructure
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Saccharomyces cerevisiae / genetics
Substances
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Antineoplastic Agents
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Cation Transport Proteins
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Copper Transporter 1
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Recombinant Proteins
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SLC31A1 protein, human
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Copper
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Cisplatin