Three-dimensional structure of the human copper transporter hCTR1
Open Access
- 17 March 2009
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (11), 4237-4242
- https://doi.org/10.1073/pnas.0810286106
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 Å. 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 hCTR1 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.Keywords
This publication has 47 references indexed in Scilit:
- Copper Transport Activity of Yeast Ctr1 Is Down-regulated via Its C Terminus in Response to Excess CopperOnline Journal of Public Health Informatics, 2009
- A place for thioether chemistry in cellular copper ion recognition and traffickingNature Chemical Biology, 2008
- Unusual Cu(I)/Ag(I) coordination of Escherichia coli CusF as revealed by atomic resolution crystallography and X‐ray absorption spectroscopyProtein Science, 2007
- Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypesJournal of Medical Genetics, 2007
- The roles of copper transporters in cisplatin resistanceCancer and Metastasis Reviews, 2007
- Copper entry into human cells: progress and unanswered questionsBioMetals, 2007
- Structure and Mechanism of the Lactose Permease of Escherichia coliScience, 2003
- The Structure of the Potassium Channel: Molecular Basis of K + Conduction and SelectivityScience, 1998
- The CCP4 suite: programs for protein crystallographyActa crystallographica. Section D, Structural biology, 1994
- Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopyJournal of Molecular Biology, 1990