LIFE SCIENCES

Sazanov Group

Structural Biology of Membrane Protein Complexes

Membrane proteins are responsible for many fundamental cellular processes including the transport of ions and metabolites, energy conversion, and signal transduction. They are the target of about two thirds of modern drugs. However, membrane proteins, especially large complexes, are challenging for structural studies and so are underrepresented in structural databases.

The Sazanov group has long been interested in the structural biology of membrane proteins. The main emphasis has been on complex I of the respiratory chain, a huge (~1 MDa) enzyme central to cellular energy production. So far, they have determined all the first atomic structures of complex I, from bacterial to the more elaborate mammalian version. The structures suggest a unique mechanism of proton translocation, which they are studying using both X-ray crystallography and cryo-electron microscopy. They are also investigating other related membrane protein complexes, such as antiporters. Their studies will help to understand the molecular design of some of the most intricate biological machines. Medical implications are multifaceted and the Sazanov group is interested in developing potential drug candidates.

Group Leader


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Team


Current Projects

Mechanism of coupling between electron transfer and proton translocation in complex I | Structure and function of mitochondrial respiratory supercomplexes | Structure and function of other membrane protein complexes relevant to bioenergetics


Publications

Fiedorczuk K, Sazanov LA. 2018. Mammalian mitochondrial complex I structure and disease causing mutations. Trends in Cell Biology. 28(10), 835–867. View

Sazanov LA. 2017. Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions. Mechanisms of primary energy transduction in biology . Mechanisms of Primary Energy Transduction in Biology 25–59. View

Letts JA, Sazanov LA. 2017. Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain. Nature Structural and Molecular Biology. 24(10), 800–808. View

Hardie R, Van Dam E, Cowley M, Han T, Balaban S, Pajic M, Pinese M, Iconomou M, Shearer R, Mckenna J, Miller D, Waddell N, Pearson J, Grimmond S, Sazanov LA, Biankin A, Villas Boas S, Hoy A, Turner N, Saunders D. 2017. Mitochondrial mutations and metabolic adaptation in pancreatic cancer. Cancer & Metabolism. 5(2). View

Gutierrez-Fernandez J, Saleh M, Alcorlo M, Gómez Mejóa A, Pantoja Uceda D, Treviño M, Vob F, Abdullah M, Galán Bartual S, Seinen J, Sánchez Murcia P, Gago F, Bruix M, Hammerschmidt S, Hermoso J. 2016. Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. 6. View

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Career

since 2015 Professor, IST Austria
2006 – 2015 Program Leader, MRC Mitochondrial Biology Unit, Cambridge, UK
2000 – 2006 Group Leader, MRC Mitochondrial Biology Unit, Cambridge, UK
1997 – 2000 Research Associate, MRC Laboratory of Molecular Biology, Cambridge, UK
1994 – 1997 Research Fellow, Imperial College, London, UK
1992 – 1994 Postdoc, University of Birmingham, UK
1990 – 1992 Postdoc, Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia
1990 PhD, Moscow State University, Russia


Selected Distinctions

2018 Member, EMBO
2016 Academic Editor, Cell Stress
2013 Member of Faculty of 1000
2012 EMBO Grant
2004 Royal Society Grant
2002 Royal Society Grant
1992 Wellcome Trust Fellowship


Additional Information

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