Donnerstag, 21. April 2016, 17:00 - 18:15 iCal

Guest Lecture by Prof. Leonid SAZANOV, IST-A

"Structure and mechanism of respiratory complex I, a giant molecular proton pump”

UZA 2, Hörsaal 6
Althanstraße 14, 1090 Wien


Abstract: NADH-ubiquinone oxidoreductase (complex I) is the first and largest enzyme in the respiratory chain of mitochondria and many bacteria. It couples electron transfer between NADH and ubiquinone to the translocation of four protons across the membrane. It is a major contributor to the proton flux used for ATP generation in mitochondria, being one of the key enzymes essential for life as we know it. Mutations in complex I lead to the most common human genetic disorders. It is an L-shaped assembly formed by membrane and hydrophilic arms. Mitochondrial complex I consists of 45 subunits of about 1 MDa in total, whilst the prokaryotic enzyme is simpler and generally consists of 14 conserved “core” subunits. We use the bacterial enzyme as a “minimal” model to understand the mechanism of complex I. We have determined first atomic structures of complex I, starting with the hydrophilic domain [1], followed by the membrane domain [2] and, finally, the recent structure of the entire Thermus thermophilus complex (536 kDa, 16 subunits, 9 Fe-S clusters, 64 TM helices) [3]. Structures suggest a unique mechanism of coupling between electron transfer in the hydrophilic domain and proton translocation in the membrane domain, via long-range (up to ~200 Å) conformational changes. I will discuss our current work, which is aimed at elucidating the molecular details of the coupling mechanism through determination of structures of the complex in different redox states with various bound substrates/inhibitors, using both X-ray crystallography and new cryo-EM methods.

[1] L.A. Sazanov, P. Hinchliffe, Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus, Science, 311 (2006) 1430-1436.

[2] R.G. Efremov, L.A. Sazanov, Structure of the membrane domain of respiratory complex I, Nature, 476 (2011) 414-420.

[3] R. Baradaran, J.M. Berrisford, G.S. Minhas, L.A. Sazanov, Crystal structure of the entire respiratory complex I, Nature, 494 (2013) 443-448.

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Doktoratskolleg MolTag


Susanne Menschik-Zunzer
Department of Pharmacology and Toxicology
DK Molecular Drug Targets
01 5277 55320,