1yjr

From Proteopedia

Revision as of 05:15, 13 April 2008

Template:STRUCTURE 1yjr

Solution structure of the apo form of the sixth soluble domain A69P mutant of Menkes protein

Overview

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.

Disease

Known disease associated with this structure: Cutis laxa, neonatal OMIM:[300011], Menkes disease OMIM:[300011], Occipital horn syndrome OMIM:[300011]

About this Structure

1YJR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

An atomic-level investigation of the disease-causing A629P mutant of the Menkes protein, ATP7A., Banci L, Bertini I, Cantini F, Migliardi M, Rosato A, Wang S, J Mol Biol. 2005 Sep 16;352(2):409-17. PMID:16083905 Page seeded by OCA on Sun Apr 13 08:15:11 2008