Functional Modules and Structural Basis of Conformational Coupling in Mitochondrial Complex I

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Science  01 Jul 2010:
DOI: 10.1126/science.1191046


Proton-pumping respiratory complex I is among the largest and most complicated membrane protein complexes. Its function is critical for efficient energy supply in aerobic cells and malfunctions are implicated in many neurodegenerative disorders. Here, we report the x-ray crystallographic analysis of mitochondrial complex I. The positions of all iron-sulfur clusters relative to the membrane arm were determined in the complete enzyme complex. The ubiquinone reduction site resides close to 30 Å above the membrane domain. The arrangement of functional modules suggests conformational coupling of redox chemistry with proton pumping and essentially excludes direct mechanisms. We suggest that a ~60 Å long helical transmission-element is critical for transducing conformational energy to proton-pumping elements in the distal module of the membrane arm.