2HRN

Solution Structure of Cu(I) P174L-HSco1

Summary for 2HRN

• Entry DOI: 10.2210/pdb2hrn/pdb
• Related: 2GQK 2GQL 2GQM 2GT5 2GT6 2GVP 2HRF
• Descriptor: SCO1 protein homolog, mitochondrial, COPPER (I) ION (2 entities in total)
• Functional Keywords: chaperone, mitochondrion, metal binding, disease mutation, structural genomics, structural proteomics in europe, spine, metal transport
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion: O75880
• Total number of polymer chains: 1
• Total formula weight: 19791.87

Authors

Banci, L.,Bertini, I.,Ciofi-Baffoni, S.,Leontari, I.,Martinelli, M.,Palumaa, P.,Sillard, R.,Wang, S.,Structural Proteomics in Europe (SPINE) (deposition date: 2006-07-20, release date: 2007-01-16, Last modification date: 2024-05-29)

Primary citation

Banci, L.,Bertini, I.,Ciofi-Baffoni, S.,Leontari, I.,Martinelli, M.,Palumaa, P.,Sillard, R.,Wang, S.
Human Sco1 functional studies and pathological implications of the P174L mutant.
Proc.Natl.Acad.Sci.Usa, 104:15-20, 2007

PubMed Abstract: 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.

PubMed: 17182746
DOI: 10.1073/pnas.0606189103

Experimental method

SOLUTION NMR