Projection structure of the human copper transporter CTR1 at 6-Å resolution reveals a compact trimer with a novel channel-like architecture

Stephen G. Aller, Vinzenz M. Unger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

166 Scopus citations

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-Å 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 Å 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.

Original languageEnglish (US)
Pages (from-to)3627-3632
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number10
DOIs
StatePublished - Mar 7 2006

Keywords

  • Cisplatin
  • Cryo-electron crystallography
  • Membrane protein
  • Metal transport

ASJC Scopus subject areas

  • General

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