Three-dimensional structure of the human copper transporter hCTR1

Christopher J. De Feo, Stephen G. Aller, Gnana S. Siluvai, Ninian Blackburn, Vinzenz M. Unger

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

Copper uptake proteins (CTRs), mediate cellular acquisition of the essential metal copper in all eukaryotes. Here, we report the structure of the human CTR1 protein solved by electron crystallography to an in plane resolution of 7 A. Reminiscent of the design of traditional ion channels, trimeric hCTR1 creates a pore that stretches across the membrane bilayer at the interface between the subunits. Assignment of the helices identifies the second transmembrane helix as the key element lining the pore, and reveals how functionally important residues on this helix could participate in Cu(I)-coordination during transport. Aligned with and sealing both ends of the pore, extracellular and intracellular domains of hCTRI appear to provide additional metal binding sites. Consistent with the existence of distinct metal binding sites, we demonstrate that hCTR1 stably binds 2 Cu(I)-ions through 3-coordinate Cu-S bonds, and that mutations in one of these putative binding sites results in a change of coordination chemistry.

Original languageEnglish (US)
Pages (from-to)4237-4242
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number11
DOIs
StatePublished - Mar 17 2009

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Copper
Metals
Binding Sites
Crystallography
Eukaryota
Ion Channels
Proteins
Electrons
Ions
Mutation
Membranes

Keywords

  • Copper homeostasis
  • Electron crystallography
  • EXAFS
  • Membrane protein

ASJC Scopus subject areas

  • General

Cite this

Three-dimensional structure of the human copper transporter hCTR1. / De Feo, Christopher J.; Aller, Stephen G.; Siluvai, Gnana S.; Blackburn, Ninian; Unger, Vinzenz M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 11, 17.03.2009, p. 4237-4242.

Research output: Contribution to journalArticle

De Feo, Christopher J. ; Aller, Stephen G. ; Siluvai, Gnana S. ; Blackburn, Ninian ; Unger, Vinzenz M. / Three-dimensional structure of the human copper transporter hCTR1. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 11. pp. 4237-4242.
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