TY - JOUR
T1 - Cytoplasmic domain filter function in the mechanosensitive channel of small conductance
AU - Gamini, Ramya
AU - Sotomayor, Marcos
AU - Chipot, Christophe
AU - Schulten, Klaus
N1 - Funding Information:
M.S. is a Howard Hughes Medical Institute Fellow of the Helen Hay Whitney Foundation. This work was supported by grants from the National Institutes of Health (1 R01-GM067887). Computer time was provided by the National Center for Supercomputing Applications and the Texas Advanced Computing Center via Large Resources Allocation Committee grant MCA93S028.
PY - 2011/7/6
Y1 - 2011/7/6
N2 - 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 -.
AB - 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 -.
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U2 - 10.1016/j.bpj.2011.05.042
DO - 10.1016/j.bpj.2011.05.042
M3 - Article
C2 - 21723817
AN - SCOPUS:80052511947
SN - 0006-3495
VL - 101
SP - 80
EP - 89
JO - Biophysical journal
JF - Biophysical journal
IS - 1
ER -