title: Functional modules and structural basis of conformational coupling in mitochondrial complex I.
abstract: Proton-pumping respiratory complex I is one of 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 an 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 angstroms 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 approximately 60-angstrom-long helical transmission element is critical for transducing conformational energy to proton-pumping elements in the distal module of the membrane arm.
authors.affiliation: Institute for Biochemistry and Molecular Biology, Centre for Biological Signalling Studies (BIOSS), University of Freiburg, D-79104 Freiburg, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Hunte
authors.forename: Volker
authors.initials: V
authors.lastname: Zickermann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D042967:Electron Transport Complex I / Q000737:chemistry* / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000737:chemistry; D008928:Mitochondria / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011522:Protons; D013455:Sulfur / Q000737:chemistry; D014451:Ubiquinone / Q000737:chemistry / Q000378:metabolism; D025062:Yarrowia / Q000201:enzymology*
chemical_list: D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D021122:Protein Subunits; D011522:Protons; D014451:Ubiquinone; D013455:Sulfur; D007501:Iron; D042967:Electron Transport Complex I