Bacterial mechanosensitive channels. What we can learn from a simple model system, when we design it to be more complicated

PhD ceremony: Mr. J.P. Birkner, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Bacterial mechanosensitive channels. What we can learn from a simple model system, when we design it to be more complicated

Promotor(s): prof. B. Poolman

Faculty: Mathematics and Natural Sciences

In his thesis Jan Peter Birkner reports on his new method that allows single-subunit resolution for manipulating and monitoring of the mechanosensitive channel of large conductance from Escherichia coli. He gradually changed the hydrophobicity of the pore constriction in this homopentameric protein by modifying a critical pore residue one subunit at a time.

In all kingdoms of life there are substances flowing: macroscopic streams, like blood in our arteries and veins, or water in plants, but also microscopic ones, like occurring at the interface of a single cell or within membrane channels. When we zoom-in to the latter, to the nanometer scaled ion channels and solute pores of biological membranes, we face barriers for the flow beyond obvious physical restrictions. In the narrow confinements as found in various ion channels (KcsA, nAChR, MscL), hydrophobic entities provide a strong barrier to the flow of water and ions across cellular membranes even though their geometry would theoretically not block it. These physically open, but biologically closed hydrophobic motifs are thought to maintain the inward and outward traffic through ion channels by a mechanism designated hydrophobic gating.

Birkner's experimental results suggest that both the channel opening and closing are initiated by one helix of a single subunit and that the participation of each of the five identical subunits to the structural transitions between the closed and open states is asymmetrical. The minimal change in pore hydrophobicity required for gating seems ideal for a fast and energy-efficient response to the changes in the membrane tension.