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Structural models of the human copper P-type ATPases ATP7A and ATP7B

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Harvard

Gourdon, P, Sitsel, O, Lykkegaard Karlsen, J, Birk Møller, L & Nissen, P 2012, 'Structural models of the human copper P-type ATPases ATP7A and ATP7B', Biological Chemistry, bind 393, nr. 4, s. 205-16.

APA

Gourdon, P., Sitsel, O., Lykkegaard Karlsen, J., Birk Møller, L., & Nissen, P. (2012). Structural models of the human copper P-type ATPases ATP7A and ATP7B. Biological Chemistry, 393(4), 205-16.

CBE

Gourdon P, Sitsel O, Lykkegaard Karlsen J, Birk Møller L, Nissen P. 2012. Structural models of the human copper P-type ATPases ATP7A and ATP7B. Biological Chemistry. 393(4):205-16.

MLA

Vancouver

Gourdon P, Sitsel O, Lykkegaard Karlsen J, Birk Møller L, Nissen P. Structural models of the human copper P-type ATPases ATP7A and ATP7B. Biological Chemistry. 2012;393(4):205-16.

Author

Gourdon, Pontus ; Sitsel, Oleg ; Lykkegaard Karlsen, Jesper ; Birk Møller, Lisbeth ; Nissen, Poul. / Structural models of the human copper P-type ATPases ATP7A and ATP7B. I: Biological Chemistry. 2012 ; Bind 393, Nr. 4. s. 205-16.

Bibtex

@article{d23b0f62f6c94fc4bc8b73d2802ba7b7,
title = "Structural models of the human copper P-type ATPases ATP7A and ATP7B",
abstract = "The human copper exporters ATP7A and ATP7B contain domains common to all P-type ATPases as well as class-specific features such as six sequential heavy-metal binding domains (HMBD1-HMBD6) and a type-specific constellation of transmembrane helices. Despite the medical significance of ATP7A and ATP7B related to Menkes and Wilson diseases, respectively, structural information has only been available for isolated, soluble domains. Here we present homology models based on the existing structures of soluble domains and the recently determined structure of the homologous LpCopA from the bacterium Legionella pneumophila. The models and sequence analyses show that the domains and residues involved in the catalytic phosphorylation events and copper transfer are highly conserved. In addition, there are only minor differences in the core structures of the two human proteins and the bacterial template, allowing protein-specific properties to be addressed. Furthermore, the mapping of known disease-causing missense mutations indicates that among the heavy-metal binding domains, HMBD5 and HMBD6 are the most crucial for function, thus mimicking the single or dual HMBDs found in most copper-specific P-type ATPases. We propose a structural arrangement of the HMBDs and how they may interact with the core of the proteins to achieve autoinhibition.",
keywords = "Adenosine Triphosphatases, Amino Acid Sequence, Cation Transport Proteins, Copper, Humans, Legionella pneumophila, Models, Biological, Molecular Sequence Data, Phosphorylation, Protein Structure, Secondary, Sequence Homology, Amino Acid, Structural Homology, Protein",
author = "Pontus Gourdon and Oleg Sitsel and {Lykkegaard Karlsen}, Jesper and {Birk M{\o}ller}, Lisbeth and Poul Nissen",
year = "2012",
language = "English",
volume = "393",
pages = "205--16",
journal = "Biological Chemistry",
issn = "1431-6730",
publisher = "Walter/de Gruyter GmbH & Co. KG",
number = "4",

}

RIS

TY - JOUR

T1 - Structural models of the human copper P-type ATPases ATP7A and ATP7B

AU - Gourdon, Pontus

AU - Sitsel, Oleg

AU - Lykkegaard Karlsen, Jesper

AU - Birk Møller, Lisbeth

AU - Nissen, Poul

PY - 2012

Y1 - 2012

N2 - The human copper exporters ATP7A and ATP7B contain domains common to all P-type ATPases as well as class-specific features such as six sequential heavy-metal binding domains (HMBD1-HMBD6) and a type-specific constellation of transmembrane helices. Despite the medical significance of ATP7A and ATP7B related to Menkes and Wilson diseases, respectively, structural information has only been available for isolated, soluble domains. Here we present homology models based on the existing structures of soluble domains and the recently determined structure of the homologous LpCopA from the bacterium Legionella pneumophila. The models and sequence analyses show that the domains and residues involved in the catalytic phosphorylation events and copper transfer are highly conserved. In addition, there are only minor differences in the core structures of the two human proteins and the bacterial template, allowing protein-specific properties to be addressed. Furthermore, the mapping of known disease-causing missense mutations indicates that among the heavy-metal binding domains, HMBD5 and HMBD6 are the most crucial for function, thus mimicking the single or dual HMBDs found in most copper-specific P-type ATPases. We propose a structural arrangement of the HMBDs and how they may interact with the core of the proteins to achieve autoinhibition.

AB - The human copper exporters ATP7A and ATP7B contain domains common to all P-type ATPases as well as class-specific features such as six sequential heavy-metal binding domains (HMBD1-HMBD6) and a type-specific constellation of transmembrane helices. Despite the medical significance of ATP7A and ATP7B related to Menkes and Wilson diseases, respectively, structural information has only been available for isolated, soluble domains. Here we present homology models based on the existing structures of soluble domains and the recently determined structure of the homologous LpCopA from the bacterium Legionella pneumophila. The models and sequence analyses show that the domains and residues involved in the catalytic phosphorylation events and copper transfer are highly conserved. In addition, there are only minor differences in the core structures of the two human proteins and the bacterial template, allowing protein-specific properties to be addressed. Furthermore, the mapping of known disease-causing missense mutations indicates that among the heavy-metal binding domains, HMBD5 and HMBD6 are the most crucial for function, thus mimicking the single or dual HMBDs found in most copper-specific P-type ATPases. We propose a structural arrangement of the HMBDs and how they may interact with the core of the proteins to achieve autoinhibition.

KW - Adenosine Triphosphatases

KW - Amino Acid Sequence

KW - Cation Transport Proteins

KW - Copper

KW - Humans

KW - Legionella pneumophila

KW - Models, Biological

KW - Molecular Sequence Data

KW - Phosphorylation

KW - Protein Structure, Secondary

KW - Sequence Homology, Amino Acid

KW - Structural Homology, Protein

M3 - Journal article

C2 - 23029640

VL - 393

SP - 205

EP - 216

JO - Biological Chemistry

JF - Biological Chemistry

SN - 1431-6730

IS - 4

ER -

ID: 36883415