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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.




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

Zhao Z, Vercellino I, Knoppová J, Sobotka R, Murray JW, Nixon PJ, Sazanov LA, Komenda J. 2023. The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis. Nature Communications. 14, 4681. View

Sazanov LA. 2023. From the ‘black box’ to ‘domino effect’ mechanism: What have we learned from the structures of respiratory complex I. The Biochemical Journal. 480(5), 319–333. View

Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov LA. 2022. A universal coupling mechanism of respiratory complex I. Nature. 609(7928), 808–814. View

Molina-Granada D, González-Vioque E, Dibley MG, Cabrera-Pérez R, Vallbona-Garcia A, Torres-Torronteras J, Sazanov LA, Ryan MT, Cámara Y, Martí R. 2022. Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit. Communications Biology. 5(1), 620. View

Kampjut D, Sazanov LA. 2022. Structure of respiratory complex I – An emerging blueprint for the mechanism. Current Opinion in Structural Biology. 74, 102350. View

View All Publications

ReX-Link: Leonid Sazanov


Career

Since 2015 Professor, Institute of Science and Technology Austria (ISTA)
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

2024 Erwin Schrödinger Prize
2023 Lower Austrian Science Award
2021 Awarded ERC Advanced Grant
2021 Awarded Keilin Memorial Medal and Lecture 2022
2019 Fellow of the Royal Society
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

Download CV
ERC Grant for “Structure and mechanism of respiratory chain molecular machines”



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