Cytoplasmic domain filter function in the mechanosensitive channel of small conductance.

Mechanosensitive channels, inner membrane proteins of bacteria, open and close in response to mechanical stimuli such as changes in membrane tension during osmotic stress. In bacteria, these channels act as safety valves preventing cell lysis upon hypoosmotic cell swelling: the channels open under membrane tension to release osmolytes along with water. The mechanosensitive channel of small conductance, MscS, consists, in addition to the transmembrane channel, of a large cytoplasmic domain (CD) that features a balloon-like, water filled chamber opening to the cytoplasm through seven side pores and a small distal pore. The CD is apparently a molecular sieve covering the channel that optimizes loss of osmolytes during osmoadaptation. We employ diffusion theory and molecular dynamics simulations to explore the transport kinetics of Glu(-) and K(+) as representative osmolytes. We suggest that the CD indeed acts as a filter that actually balances passage of Glu(-) and K(+), and possibly other positive and negative osmolytes, to yield a largely neutral efflux and, thereby, reduce cell depolarization in the open state and conserve to a large degree the essential metabolite Glu(-).