Crystal structure of a copper-transporting PIB-type ATPase
(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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- author
- Gourdon, Pontus LU ; Liu, Xiang-Yu ; Skjørringe, Tina ; Morth, J Preben ; Møller, Lisbeth Birk ; Pedersen, Bjørn Panyella and Nissen, Poul
- publishing date
- 2011-06-29
- type
- Contribution to journal
- publication status
- 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
-
- pmid:21716286
- 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
- 2024-12-10 10:44:40
@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}},
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}},
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}},
doi = {{10.1038/nature10191}},
volume = {{475}},
year = {{2011}},
}