Crystal structure of a copper-transporting PIB-type ATPase
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Crystal structure of a copper-transporting PIB-type ATPase. / Gourdon, Pontus Emanuel; Liu, Xiang-Yu; Skjørringe, Tina; Morth, J Preben; Møller, Lisbeth Birk; Pedersen, Bjørn Panyella; Nissen, Poul.
I: Nature, Bind 475, Nr. 7354, 07.07.2011, s. 59-64.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Crystal structure of a copper-transporting PIB-type ATPase
AU - Gourdon, Pontus Emanuel
AU - Liu, Xiang-Yu
AU - Skjørringe, Tina
AU - Morth, J Preben
AU - Møller, Lisbeth Birk
AU - Pedersen, Bjørn Panyella
AU - Nissen, Poul
N1 - ©2011 Macmillan Publishers Limited. All rights reserved
PY - 2011/7/7
Y1 - 2011/7/7
N2 - 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.
AB - 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.
KW - Adenosine Triphosphatases
KW - Bacterial Proteins
KW - Binding Sites
KW - Biological Transport
KW - Calcium
KW - Cation Transport Proteins
KW - Cell Membrane
KW - Copper
KW - Crystallography, X-Ray
KW - Cytoplasm
KW - Hepatolenticular Degeneration
KW - Humans
KW - Legionella pneumophila
KW - Menkes Kinky Hair Syndrome
KW - Models, Molecular
KW - Mutation, Missense
KW - Protein Structure, Tertiary
KW - Sarcoplasmic Reticulum Calcium-Transporting ATPases
KW - Structure-Activity Relationship
U2 - 10.1038/nature10191
DO - 10.1038/nature10191
M3 - Journal article
C2 - 21716286
VL - 475
SP - 59
EP - 64
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7354
ER -
ID: 126103702