1YJT: Solution structure of the Cu(I) form of the sixth soluble domain A69P mutant of Menkes protein

Menkes disease is a fatal disease that can be induced by various mutations in the ATP7A gene, leading to unpaired uptake of dietary copper. The ATP7A gene encodes a copper(I)-translocating ATPase. Here the disease-causing A629P mutation, which occurs in the last of the six copper(I)-binding soluble domains of the ATPase (hereafter MNK6), was investigated. To understand why this apparently minor amino acid replacement is pathogenic, the solution structures and dynamics on various time-scales of wild-type and A629P-MNK6 were determined both in the apo- and copper(I)-loaded forms. The interaction in vitro with the physiological ATP7A copper(I)-donor (HAH1) was additionally studied. The A629P mutation makes the protein beta-sheet more solvent accessible, possibly resulting in an enhanced susceptibility of ATP7A to proteolytic cleavage and/or in reduced capability of copper(I)-translocation. A small reduction of the affinity for copper(I) is also observed. Both effects could concur to pathogenicity.
PDB ID: 1YJTDownload
MMDB ID: 36613
PDB Deposition Date: 2005/1/15
Updated in MMDB: 2012/11
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Molecular Components in 1YJT
Label Count Molecule
Protein (1 molecule)
Copper-transporting Atpase 1(Gene symbol: ATP7A)
Molecule annotation
Chemical (1 molecule)
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