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Structure and mechanism of membrane-embedded molecular machines

Date: Monday, May 13, 2019 16:00 - 17:00
Speaker: Leonid Sazanov (IST Austria)
Location: Raiffeisen Lecture Hall, Central Building
Series: 4th year colloquium
Host: Michael Sixt
Contact: Arinya Eller
Central building lecture hall

Membrane proteins are responsible for many fundamental cellular processes including the transport of ions and metabolites, energy conversion and signal transduction. Many of these proteins work as molecular machines, employing large-scale motions to perform their function. We are interested in the structure and function of such machines, mainly from the domain of bioenergetics (i.e. biological energy conversion, such as in respiration and photosynthesis).

Respiratory chain of mitochondria and bacteria, responsible for most of energy production in the cell, comprises a series of such machines (complexes I-V) working in concert to produce ATP (universal biological energy carrier). Complex I is the first and the largest enzyme in the chain, coupling electron transfer between two substrates to the translocation of four protons across the membrane. Previously we have determined the first atomic structure of complex I, using X-ray crystallography on bacterial enzyme. More recently, after the move to IST, we have solved the first structure of the even larger (1 MDa, 45 subunits) mammalian complex I, using new cryoEM methods. In mitochondria respiratory complexes are organised into supercomplexes, or respirasomes, and we have solved structures of these supercomplexes, also using cryoEM. Current work is centred on the deciphering of the enigmatic coupling mechanism of complex I and on the functional role of the supercomplexes. Apart from complex I, we are working also on other intriguing molecular machines, such as ATPase (complex V), MRP antiporters and proton-translocating transhydrogenase.

Each of these biological machines employs unique mechanism, resembling engineering creations, such as turbine or steam engine. Each new structure brings a lot of surprises, showing Nature’s ingenuity in efficiently implementing different pathways necessary for life.

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