Data from: Force transduction and lipid binding in MscL: a continuum-molecular approach

The bacterial mechanosensitive channel MscL, a small protein mainly
activated by membrane tension, is a central model system to study the
transduction of mechanical stimuli into chemical signals. Mutagenic
studies suggest that MscL gating strongly depends on both intra-protein
and interfacial lipid-protein interactions. However, there is a gap
between this detailed chemical information and current mechanical models
of MscL gating. Here, we investigate the MscL bilayer-protein interface
through molecular dynamics simulations, and take a combined
continuum-molecular approach to connect chemistry and mechanics. We
quantify the effect of membrane tension on the forces acting on the
surface of the channel, and identify interactions that may be critical in
the force transduction between the membrane and MscL. We find that the
local stress distribution on the protein surface is largely asymmetric,
particularly under tension, with the cytoplasmic side showing
significantly larger and more localized forces, which pull the protein
radially outward. The molecular interactions that mediate this behavior
arise from hydrogen bonds between the electronegative oxygens in the lipid
headgroup and a cluster of positively charged lysine residues on the
amphipathic S1 domain and the C-terminal end of the second trans-membrane
helix. We take advantage of this strong interaction (estimated to be 10–13
kT per lipid) to actuate the channel (by applying forces on protein-bound
lipids) and explore its sensitivity to the pulling magnitude and
direction. We conclude by highlighting the simple motif that confers MscL
with strong anchoring to the bilayer, and its presence in various integral
membrane proteins including the human mechanosensitive channel K2P1 and
bovine rhodopsin.