PMID- 17182746
OWN - NLM
STAT- MEDLINE
DCOM- 20070207
LR  - 20201209
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 104
IP  - 1
DP  - 2007 Jan 2
TI  - Human Sco1 functional studies and pathological implications of the P174L mutant.
PG  - 15-20
AB  - 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.
FAU - Banci, Lucia
AU  - Banci L
AD  - Magnetic Resonance Center (CERM) and Department of Chemistry, University of 
      Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Florence, Italy.
FAU - Bertini, Ivano
AU  - Bertini I
FAU - Ciofi-Baffoni, Simone
AU  - Ciofi-Baffoni S
FAU - Leontari, Iliana
AU  - Leontari I
FAU - Martinelli, Manuele
AU  - Martinelli M
FAU - Palumaa, Peep
AU  - Palumaa P
FAU - Sillard, Rannar
AU  - Sillard R
FAU - Wang, Shenlin
AU  - Wang S
LA  - eng
SI  - PDB/2HRN
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061220
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Membrane Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (SCO1 protein, human)
RN  - 789U1901C5 (Copper)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Copper/metabolism
MH  - Electron Transport Complex IV/chemistry
MH  - Humans
MH  - Membrane Proteins/*chemistry/*physiology
MH  - Molecular Chaperones
MH  - Mutation
MH  - Oxidation-Reduction
MH  - Protein Conformation
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - Structure-Activity Relationship
PMC - PMC1765425
COIS- The authors declare no conflict of interest.
EDAT- 2006/12/22 09:00
MHDA- 2007/02/08 09:00
PMCR- 2007/07/02
CRDT- 2006/12/22 09:00
PHST- 2006/12/22 09:00 [pubmed]
PHST- 2007/02/08 09:00 [medline]
PHST- 2006/12/22 09:00 [entrez]
PHST- 2007/07/02 00:00 [pmc-release]
AID - 0606189103 [pii]
AID - 4486 [pii]
AID - 10.1073/pnas.0606189103 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):15-20. doi: 10.1073/pnas.0606189103. 
      Epub 2006 Dec 20.