Professor Steven B. Vik, Southern Methodist University, Texas, USA.
E. coli Complex I: Assembling and Constraining a Dynamic Proton Pump.
Complex I, a commonly found enzyme of electron transport chains, couples the NADH-driven reduction of ubiquinone to the translocation of protons against an electrochemical proton gradient. In E. coli, the enzyme is formed by 13 subunits, arranged in 2 distinct arms: a peripheral arm that binds NADH and reduces quinones, and an integral membrane arm that pumps protons. Due to the large distances between quinone reduction and the sites of proton translocation, it is expected that a series of conformational changes are essential. The reported crystal structures of bacterial Complex I have revealed interesting structural features of this enzyme. Each site of proton pumping appears to consist of two offset, half channels connected by a perpendicular passage. Three of the sites appear to be linked through a long 75-residue, surface alpha-helix that was proposed to have a piston-like function. Cysteine substitution mutagenesis has been used to provide sites for cross-linking to constrain conformational changes. The results indicate that the long lateral helix does not need to make significant movement during the turnover of the enzyme. Other cross-links within and between membrane subunits suggest regions where conformational changes are important for proton pumping. Future work seeks to identify the assembly pathways of the enzyme, and to understand how mutations discovered in humans disrupt assembly.
ABOUT THE PRESENTER
Steven Vik is a professor at the Department of Biological Sciences, Southern Methodist University in Dallas, Texas, USA. He received his B.S. from the California Institute of Technology and Ph.D from the University of Oregon. Postdoctoral research was conducted at Scripps Institute and at Stanford University. He has been a visiting scholar at the Academy of Sciences, Beijing China, and University of Osnabrück, Germany, and was a visiting professor at Zhejiang University, Hangzhou China, 2008-2010. He has been at Southern Methodist University since 1987. During his career he has studied the structure, function and assembly of enzymes of oxidative phosphorylation, including cytochrome oxidase and Complex II of mammalian mitochondria, and the ATP synthase and Complex I of bacteria. His lab is currently working on the assembly of bacterial Complex I, and how human mutations might affect function and assembly as revealed by that system.
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