2KIJ

Solution structure of the Actuator domain of the copper-transporting ATPase ATP7A

Summary for 2KIJ

• Entry DOI: 10.2210/pdb2kij/pdb
• NMR Information: BMRB: 16277
• Descriptor: Copper-transporting ATPase 1 (1 entity in total)
• Functional Keywords: actuator, atp7a, menkes disease, alternative splicing, atp-binding, cell membrane, copper, copper transport, cytoplasm, disease mutation, endoplasmic reticulum, glycoprotein, golgi apparatus, hydrolase, ion transport, magnesium, membrane, metal-binding, nucleotide-binding, phosphoprotein, polymorphism, transmembrane, transport
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 12967.74

Authors

Banci, L.,Bertini, I.,Cantini, F.,Migliardi, M.,Nushi, F.,Natile, G.,Rosato, A. (deposition date: 2009-05-06, release date: 2009-08-25, Last modification date: 2024-05-15)

Primary citation

Banci, L.,Bertini, I.,Cantini, F.,Migliardi, M.,Natile, G.,Nushi, F.,Rosato, A.
Solution structures of the actuator domain of ATP7A and ATP7B, the Menkes and Wilson disease proteins
Biochemistry, 48:7849-7855, 2009

PubMed Abstract: ATP7A and ATP7B are two human P(1B)-type ATPases that have a crucial role in maintaining copper(I) homeostasis. Among the various domains of these enzymes, one, called the Actuator or A-domain, has a regulatory function and is required for the phosphatase step of the catalytic cycle (dephosphorylation of the intermediate formed during ATP hydrolysis). Here we report the solution structures of the A-domain of both proteins, solved by heteronuclear NMR spectroscopy and a characterization of the dynamics of the A-domain of ATP7A. We observed that the catalytically important TGE loop protrudes from the structure ready for interaction with the phosphorylated site in the ATP-binding domain. The loop is rigid, suggesting that the catalytic step does not require substantial structural flexibility or rearrangements. The present structures were useful to rationalize the molecular effects of disease-causing mutations. In particular, it can be concluded that mutations occurring in the A-domain either destabilize the fold of the domain (such as Gly860Val in ATP7A) or affect the network of communication within the domain (such as Leu873Arg in ATP7A) or with the other domains of the enzyme (such as Gly853Arg in ATP7A).

PubMed: 19645496
DOI: 10.1021/bi901003k

Experimental method

SOLUTION NMR