Our aim is to understand how large molecular machines work. To achieve this we are using transmission electron cryogenic microscopy (cryo-EM) and methods of single particle analysis to determine the structures of the molecular machines and to resolve their functionally important conformational states.
Many large protein complexes resemble human-made machines and mechanisms. Activity of these proteins is associated with large-scale conformational changes. We want to determine the structure of these protein complexes and see their conformation changes when they work. Due to intrinsic flexibility, molecular machines are often difficult to crystallize. To determine their 3D structure we use a method of single particle cryo-EM, which does not require crystals.
We focus primarily on the structures of large membrane protein complexes involved in trans-membrane ion transport. We want to determine their high-resolution structures in functionally important conformational states. This will allow us to understand how numerous factors alter protein conformation and regulate the trans-membrane ion transport.
The method of cryo-EM has a high potential for solving atomic resolution structures of large and intermediate sized protein complexes. Our second focus is related to the further development of the single particle analysis method, in particular techniques of sample preparation and image processing. Our goal is to determine the high-resolution 3D structures of specific conformational intermediates of protein complexes, inducing short-living intermediates and high-resolution structures of flexible protein complexes.
- A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover. (Nat Commun, 8, 1008, 2017)
- A long road towards the structure of respiratory complex I, a giant molecular proton pump. (Biochem Soc Trans, 41, 1265-71, 2013)
- Structure of the membrane domain of respiratory complex I. (Nature, 476, 414-20, 2011)
- The architecture of respiratory complex I. (Nature, 465, 441-5, 2010)
- Time-resolved microspectroscopy on a single crystal of bacteriorhodopsin reveals lattice-induced differences in the photocycle kinetics. (Biophys J, 91, 1441-51, 2006)
- Development of the signal in sensory rhodopsin and its transfer to the cognate transducer. (Nature, 440, 115-9, 2006)