Membrane tension, lipid adaptation, conformational changes, and energetics in MscL gating.
Membrane tension, lipid adaptation, conformational changes, and energetics in MscL gating.
复制标题
MscL 门控中的膜张力、脂质适应、构象变化和能量学。
DOI：
10.1016/j.bpj.2011.06.029
复制
发表时间：
2011
影响因子：
3.4
通讯作者：
Im,Wonpil
中科院分区：
文献类型：
--
作者：
Rui,Huan;Kumar,Ritesh;Im,Wonpil
This study aims to explore gating mechanisms of mechanosensitive channels in terms of membrane tension, membrane adaptation, protein conformation, and energetics. The large conductance mechanosensitive channel fromMycobacterium tuberculosis(Tb-MscL) is used as a model system; Tb-MscL acts as a safety valve by releasing small osmolytes through the channel opening under extreme hypoosmotic conditions. Based on the assumption that the channel gating involves tilting of the transmembrane (TM) helices, we have performed free energy simulations of Tb-MscL as a function of TM helix tilt angle in a dimyristoylphosphatidylcholine bilayer. Based on the change in system dimensions, TM helix tilting is shown to be essentially equivalent to applying an excess surface tension to the membrane, causing channel expansion, lipid adaptation, and membrane thinning. Such equivalence is further corroborated by the observation that the free energy cost of Tb-MscL channel expansion is comparable to the work done by the excess surface tension. Tb-MscL TM helix tilting results in an expanded water-conducting channel of an outer dimension similar to the proposed fully open MscL structure. The free energy decomposition indicates a possible expansion mechanism in which tilting and expanding of TM2 facilitates the iris-like motion of TM1, producing an expanded Tb-MscL.
