Crystal structure of a copper-transporting PIB-type ATPase

Pontus Emanuel Gourdon; Xiang-Yu Liu; Tina Skjørringe; J Preben Morth; Lisbeth Birk Møller; Bjørn Panyella Pedersen; Poul Nissen

doi:10.1038/nature10191

Crystal structure of a copper-transporting PIB-type ATPase

Pontus Emanuel Gourdon, Xiang-Yu Liu, Tina Skjørringe, J Preben Morth, Lisbeth Birk Møller, Bjørn Panyella Pedersen, Poul Nissen

Inflammation, Metabolism and Oxidation

223 Citationer (Scopus)

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 Ã.. 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 Wilsong's diseases.

Originalsprog	Engelsk
Tidsskrift	Nature
Vol/bind	475
Udgave nummer	7354
Sider (fra-til)	59-64
Antal sider	6
ISSN	0028-0836
DOI	https://doi.org/10.1038/nature10191
Status	Udgivet - 7 jul. 2011

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title = "Crystal structure of a copper-transporting PIB-type ATPase",

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 {\~A}.. 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 Wilsong's diseases.",

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",

author = "Gourdon, {Pontus Emanuel} and Xiang-Yu Liu and Tina Skj{\o}rringe and Morth, {J Preben} and M{\o}ller, {Lisbeth Birk} and Pedersen, {Bj{\o}rn Panyella} and Poul Nissen",

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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

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 Ã.. 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 Wilsong'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 Ã.. 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 Wilsong'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

SN - 0028-0836

VL - 475

SP - 59

EP - 64

JO - Nature

JF - Nature

IS - 7354

ER -

Crystal structure of a copper-transporting PIB-type ATPase

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