A long road towards the structure of respiratory complex I, a giant molecular proton pump

• DOI: 10.1042/bst20130193
• Publication Date: 2013-09-23T15:37:32Z
• Authors: Leonid A. Sazanov; Rozbeh Baradaran; Rouslan G. Efremov; John M. Berrisford; Gurdeep Minhas
• Keywords: Thermus thermophilus

Complex I (NADH:ubiquinone oxidoreductase) is central to cellular energy production, being the first and largest enzyme of respiratory chain in mitochondria. It couples electron transfer from NADH ubiquinone with proton translocation across inner mitochondrial membrane involved a wide range human neurodegenerative disorders. Mammalian complex composed 44 different subunits, whereas ‘minimal’ bacterial version contains 14 highly conserved ‘core’ subunits. The L-shaped assembly consists hydrophilic domains. We have determined all known atomic structures I, starting domain Thermus thermophilus (eight nine Fe–S clusters), followed by domains Escherichia coli (six 55 transmembrane helices) T. (seven 64 enzymes, finally culminating recent crystal structure entire intact (536 kDa, 16 clusters, helices). suggests an unusual unique coupling mechanism via long-range conformational changes. Determination was possible only through this step-by-step approach, building on smaller subcomplexes towards assembly. Large proteins are notoriously difficult crystallize, so various non-standard sometimes counterintuitive approaches were employed order achieve diffraction high resolution solve structures. These steps, as well implications final structure, discussed present review.