From membrane tension to channel gating: A principal energy transfer mechanism for mechanosensitive channels

Abstract

Mechanosensitive (MS) channels are evolutionarily conserved membrane proteins that play essential roles in multiple cellular processes, including sensing mechanical forces and regulating osmotic pressure. Bacterial MscL and MscS are two prototypes of MS channels. Numerous structural studies, in combination with biochemical and cellular data, provide valuable insights into the mechanism of energy transfer from membrane tension to gating of the channel. We discuss these data in a unified two-state model of thermodynamics. In addition, we propose a lipid diffusion-mediated mechanism to explain the adaptation phenomenon of MscS.

Keywords: gating mechanism; lipid-protein interaction; mechanosensitive channels; membrane tension sensing; osmoregulation.

Figure 1

Schematic diagram of pressure profile and tension distribution. The lateral pressure (p) as a function of position z along the membrane normal is presented on the left side. Tension forces applied on the embedded membrane protein is schematically presented on the right side. Sections near the aqueous‐membrane interface are in cyan, and sections buried inside the membrane are shown in orange.

Figure 2

Crystal structures of Ma‐MscL and Ec‐MscS at different conformational states. A: Ma‐MscL structures in the closed state (PDB ID: 4Y7K) and expanded state (PDB ID: 4Y7J). B: Ec‐MscS structures in the closed/inactive state (PDB ID: 2OAU) and open state (obtained from A106V mutant, PDB ID: 2VV5). In each of the two panels, a representative protomer is shown in gold color.

Figure 3

Model of putative opening mechanism of MS channels. In each of the MscL (A) and MscS (B) case, a representative pore‐forming helix is shown in red. The surface tension associated forces are indicated with thin‐line arrows. The tilting of the pore‐forming helix is indicated by the thick pink arrow. In the case of MscL, the overall rotations of top and bottom parts of the channel complex are indicated.

Figure 4

Putative mechanism of adaptation of MscS. A: Schematics of lipid penetration. B: Channel connections within the Ec‐MscS complex. TM helices (orange ribbons) are obtained from the crystal structure of the open form (PDB ID: 2VV5). The complex is viewed from the cytosolic side, with cytosolic domains removed for clarity. Channels within the TM complex were calculated with probes of 1.4 Å radius and illustrated with green meshes. The central pore, clefts between TM3a helices, and valleys between TM1‐TM2 hairpins are marked with a star, diamond symbols, and triangle symbols, respectively.