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Crystal structure of a copper-transporting PIB-type ATPase

Gourdon, Pontus LU ; Liu, Xiang-Yu; Skjørringe, Tina; Morth, J Preben; Møller, Lisbeth Birk; Pedersen, Bjørn Panyella and Nissen, Poul (2011) In Nature 475(7354). p.59-64
Abstract

Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu(+)-ATPase, in a copper-free form, as determined by X-ray crystallography at 3.2 Å resolution. The structure indicates a three-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to Ca(2+)-ATPase suggest an ATPase-coupled copper release mechanism from the... (More)

Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu(+)-ATPase, in a copper-free form, as determined by X-ray crystallography at 3.2 Å resolution. The structure indicates a three-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to Ca(2+)-ATPase suggest an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. The structure also provides a framework to analyse missense mutations in the human ATP7A and ATP7B proteins associated with Menkes' and Wilson's diseases.

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published
keywords
Adenosine Triphosphatases, Bacterial Proteins, Binding Sites, Biological Transport, Calcium, Cation Transport Proteins, Cell Membrane, Copper, Crystallography, X-Ray, Cytoplasm, Hepatolenticular Degeneration, Humans, Legionella pneumophila, Menkes Kinky Hair Syndrome, Models, Molecular, Mutation, Missense, Protein Structure, Tertiary, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Structure-Activity Relationship, Journal Article, Research Support, Non-U.S. Gov't
in
Nature
volume
475
issue
7354
pages
59 - 64
publisher
Nature Publishing Group
external identifiers
  • scopus:79960033247
ISSN
0028-0836
DOI
10.1038/nature10191
language
English
LU publication?
no
id
f5085167-efb6-42fe-8849-4c53d78077af
date added to LUP
2017-04-29 15:31:24
date last changed
2017-11-19 04:39:38
@article{f5085167-efb6-42fe-8849-4c53d78077af,
  abstract     = {<p>Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu(+)-ATPase, in a copper-free form, as determined by X-ray crystallography at 3.2 Å resolution. The structure indicates a three-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to Ca(2+)-ATPase suggest an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. The structure also provides a framework to analyse missense mutations in the human ATP7A and ATP7B proteins associated with Menkes' and Wilson's diseases.</p>},
  author       = {Gourdon, Pontus and Liu, Xiang-Yu and Skjørringe, Tina and Morth, J Preben and Møller, Lisbeth Birk and Pedersen, Bjørn Panyella and Nissen, Poul},
  issn         = {0028-0836},
  keyword      = {Adenosine Triphosphatases,Bacterial Proteins,Binding Sites,Biological Transport,Calcium,Cation Transport Proteins,Cell Membrane,Copper,Crystallography, X-Ray,Cytoplasm,Hepatolenticular Degeneration,Humans,Legionella pneumophila,Menkes Kinky Hair Syndrome,Models, Molecular,Mutation, Missense,Protein Structure, Tertiary,Sarcoplasmic Reticulum Calcium-Transporting ATPases,Structure-Activity Relationship,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {06},
  number       = {7354},
  pages        = {59--64},
  publisher    = {Nature Publishing Group},
  series       = {Nature},
  title        = {Crystal structure of a copper-transporting PIB-type ATPase},
  url          = {http://dx.doi.org/10.1038/nature10191},
  volume       = {475},
  year         = {2011},
}