2hrf
From Proteopedia
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'''Solution Structure of Cu(I) P174L HSco1''' | '''Solution Structure of Cu(I) P174L HSco1''' | ||
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[[Category: Wang, S.]] | [[Category: Wang, S.]] | ||
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| - | [[Category: | + | [[Category: Structural genomic]] |
| - | [[Category: | + | [[Category: Structural proteomics in europe]] |
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Revision as of 05:20, 13 April 2008
Solution Structure of Cu(I) P174L HSco1
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.
About this Structure
2HRF is a Single protein structure of sequence from Homo sapiens. 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 Page seeded by OCA on Sun Apr 13 08:20:13 2008
Categories: Homo sapiens | Single protein | Banci, L. | Bertini, I. | Ciofi-Baffoni, S. | Leontari, I. | Martinelli, M. | Palumaa, P. | SPINE, Structural Proteomics in Europe. | Sillard, R. | Wang, S. | 3d-structure | Chaperone | Disease mutation | Metal-binding | Mitochondrion | Spine | Structural genomic | Structural proteomics in europe
