Chloride channels belong to an extensive family of transmembrane proteins, whose dysfunction causes a wide range of illnesses [1]. A detailed study of the structural changes during transport enables us to understand the transport mechanism and can provide valuable information required for effective treatment.
Bacterial chloride channel from E. coli (ClC-ec1), whose structure has been solved by X-ray crystallography, is widely used as a model protein for studies of the transport mechanism. ClC-ec1 is a homodimer and each of its subunits consist of two topologically related domains in an antiparallel architecture arrangement [2]. This so called ‘’inverted topology repeats’’ propose existence of an ‘outward-facing’ (OF) and an ‘inward-facing’ (IF) shapes. However the crystal structure traps the protein in an occluded state.
In a recent work [3], Khantwal, Abraham et al. have discovered new previously uncharacterized ‘outward-facing open’ state using cross-linking of Y419C and D417C mutants studied by NMR and DEER techniques. Our aim is to obtain more information about this new state by use of hydrogen/deuterium exchange that enables us to monitor dynamic conformational changes under different conditions (pH, various concentrations of chloride anions) directly in solution.
Financial support from Charles University in Prague (GA UK no. 389115) and European Regional Development Funds (CZ.1.05/1.1.00/02.0109) is gratefully acknowledged.