An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR.
The oxidative folding mechanism in the intermembrane space of human mitochondria underpins a disulfide relay system consisting of the import receptor Mia40 and the homodimeric FAD-dependent thiol oxidase ALR. The flavoprotein ALR receives two electrons per subunit from Mia40, which are then donated through one-electron reactions to two cytochrome c molecules, thus mediating a switch from two-electron to one-electron transfer. We dissect here the mechanism of the electron flux within ALR, characterizing at the atomic level the ALR intermediates that allow electrons to rapidly flow to cytochrome c. The intermediate critical for the electron-transfer process implies the formation of a specific inter-subunit disulfide which exclusively allows electron flow from Mia40 to FAD. This finding allows us to present a complete model for the electron-transfer pathway in ALR.
Magnetic Resonance Center, University of Florence, via L. Sacconi 6, Sesto Fiorentino, Italy. banci@cerm.unifi.it
Lucia
L
Banci
Ivano
I
Bertini
Vito
V
Calderone
Chiara
C
Cefaro
Simone
S
Ciofi-Baffoni
Angelo
A
Gallo
Kostas
K
Tokatlidis
D002942:Circular Dichroism; D003579:Cytochrome Reductases / Q000737:chemistry / Q000378:metabolism*; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism*; D004579:Electron Transport; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008958:Models, Molecular; D010084:Oxidation-Reduction; D050862:Oxidoreductases Acting on Sulfur Group Donors; D013056:Spectrophotometry, Ultraviolet
C507282:CHCHD4 protein, human; D004220:Disulfides; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D045304:Cytochromes c; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors