2hrf

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Solution Structure of Cu(I) P174L HSco1

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The pathogenic mutant (P174L) of human Sco1 produces respiratory chain, deficiency associated with cytochrome c oxidase (CcO) assembly defects., The solution structure of the mutant in its Cu(I) form shows that Leu-174, prevents the formation of a well packed hydrophobic region around the, metal-binding site and causes a reduction of the affinity of copper(I) for, the protein. K(D) values for Cu(I)WT-HSco1 and Cu(I)P174L-HSco1 are, approximately 10(-17) and approximately 10(-13), respectively. The, reduction potentials of the two apo proteins are similar, but slower, reduction/oxidation rates are found for the mutant with respect to the WT., The mitochondrial metallochaperone in the partially oxidized, Cu(1)(I)Cox17(2S-S) form, at variance with the fully reduced, Cu(4)(I)Cox17, interacts transiently with both WT-HSco1 and the mutant, forming the Cox17/Cu(I)/HSco1 complex, but copper is efficiently, transferred only in the case of WT protein. Cu(1)(I)Cox17(2S-S) indeed has, an affinity for copper(I) (K(D) approximately 10(-15)) higher than that of, the P174L-HSco1 mutant but lower than that of WT-HSco1. We propose that, HSco1 mutation, altering the structure around the metal-binding site, affects both copper(I) binding and redox properties of the protein, thus, impairing the efficiency of copper transfer to CcO. The pathogenic, mutation therefore could (i) lessen the Sco1 affinity for copper(I) and, hence copper supply for CcO or (ii) decrease the efficiency of reduction, of CcO thiols involved in copper binding, or both effects could be, produced by the mutation.

Disease

Known diseases associated with this structure: Hepatic failure, early onset, and neurologic disorder OMIM:[603644]

About this Structure

2HRF is a Single protein structure of sequence from Homo sapiens with CU1 as ligand. Full crystallographic information is available from OCA.

Reference

Human Sco1 functional studies and pathological implications of the P174L mutant., Banci L, Bertini I, Ciofi-Baffoni S, Leontari I, Martinelli M, Palumaa P, Sillard R, Wang S, Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):15-20. Epub 2006 Dec 20. PMID:17182746

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