Molecular Dynamics Analysis on the Force Transmission Pathway via Inter-Subunit Pathway for Mechano-Gating of Bacterial Mechanosensitive Channel MscL

The bacterial mechanosensitive channel MscL is constituted of homopentamer of a subunit with TM1 inner and TM2 outer transmembrane helix. The major issue on MscL is to understand the gating mechanism driven by membrane tension. Upon membrane stretch, the helices are dragged by lipids at the tension sensor F78 and tilted, accompanied by outward sliding, leading to a gate expansion. To get insights into the relationship between F78 and the gate including G22, we performed MD simulations of G22N GOF and F78N LOF MscLs and G22N showed spontaneous opening without membrane stretch, while F78N could not be opened even under strong membrane tension.