Conformational pathways in the gating of Escherichia coli mechanosensitive channel.
The pathway of the gating conformational transition of Escherichia coli mechanosensitive channel was simulated, using the recently modeled open and closed structures, by targeted molecular dynamics method. The transition can be roughly viewed as a four-stage process. The initial motion under a lower tension load is predominantly elastic deformation. The opening of the inner hydrophobic pore on a higher tension load takes place after the major expansion of the outer channel dimension. The hypothetical N-terminal S1 helical bundle has been confirmed to form the hydrophobic gate, together with the M1 helices. The sequential breaking of the tandem hydrophobic constrictions on the M1 and S1 helices makes the two parts of the gate strictly coupled, acting as a single gate. The simulation also revealed that there is no significant energetic coupling between the inner S1 bundle and the outer M2 transmembrane helices. The molten-globular-like structural features of the S1 bundle in its intermediate open states may account for the observed multiple subconductance states. Moreover, the intermediate open states of mechanosensitive channels are not symmetric, i.e., the opening does not follow iris-like motion, which sharply contrasts to the potassium channel KcsA.
Kong
Yifei
Y
Graduate Program of Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, One Baylor Plaza, BCM-125, Houston, TX 77030, USA.
Shen
Yufeng
Y
Warth
Tiffany E
TE
Ma
Jianpeng
J
D003593:Cytoplasm / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D007473:Ion Channels / Q000737:chemistry*; D008958:Models, Molecular; D015221:Potassium Channels / Q000737:chemistry*; D011487:Protein Conformation; D013997:Time Factors
D029968:Escherichia coli Proteins; D007473:Ion Channels; C086596:MscL protein, E coli; D015221:Potassium Channels