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Gating of MscL studied by steered molecular dynamics
Justin Gullingsrud1, Klaus Schulten
1Department of Physics and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Biophysical Journal
|September 26, 2003
Summary
Simulations show how membrane tension opens the mechanosensitive channel of large conductance (MscL) by applying forces. This reveals an iris-like pore expansion and helix tilting mechanism for channel gating.
Area of Science:
- Biophysics
- Molecular Biology
- Membrane Protein Dynamics
Background:
- Mechanosensitive channels (MSCs) like MscL are crucial for cellular mechanotransduction.
- Understanding MscL gating is key to deciphering how cells sense and respond to mechanical forces.
Purpose of the Study:
- To investigate the mechanism by which membrane tension gates the mechanosensitive channel of large conductance (MscL).
- To elucidate how applied forces are transduced into channel opening.
Main Methods:
- Steered molecular dynamics (SMD) simulations were performed on a homology model of MscL from Escherichia coli.
- External forces (35-70 pN) were applied to residues at the membrane-water interface, mimicking membrane tension.
- Simulations were analyzed to observe channel conformational changes over a 10-ns timescale.
Main Results:
- A fully expanded, open channel state was achieved, revealing the gating mechanism.
- The gating mechanism involves an iris-like expansion of the pore and tilting of transmembrane helices.
- Force application on the cytoplasmic side facilitated channel opening, and specific residues hindering opening were identified.
Conclusions:
- Membrane tension directly gates MscL through specific force-induced conformational changes.
- The identified gating mechanism aligns with existing models of MscL function.
- Key residues influencing MscL gating by steric hindrance were pinpointed.