Abstract
The mechanosensitive channel of large conductance (MscL) is capable of transducing mechanical stimuli such as membrane tension into an electrochemical response. MscL provides a widely-studied model system for mechanotransduction and, more generally, for how bilayer mechanical properties regulate protein conformational changes. Much effort has been expended on the detailed experimental characterization of the molecular structure and biological function of MscL. However, despite its central significance, even basic issues such as the physiologically relevant oligomeric states and molecular structures of MscL remain a matter of debate. In particular, tetrameric, pentameric, and hexameric oligomeric states of MscL have been proposed, together with a range of detailed molecular structures of MscL in the closed and open channel states. Previous theoretical work has shown that the basic phenomenology of MscL gating can be understood using an elastic model describing the energetic cost of the thickness deformations induced by MscL in the surrounding lipid bilayer. Here, we generalize this elastic model to account for the proposed oligomeric states and hydrophobic shapes of MscL. We find that the oligomeric state and hydrophobic shape of MscL are reflected in the energetic cost of lipid bilayer deformations. We make quantitative predictions pertaining to the gating characteristics associated with various structural models of MscL and, in particular, show that different oligomeric states and hydrophobic shapes of MscL yield distinct membrane contributions to the gating energy and gating tension. Thus, the functional properties of MscL provide a signature of the oligomeric state and hydrophobic shape of MscL. Our results suggest that, in addition to the hydrophobic mismatch between membrane proteins and the surrounding lipid bilayer, the symmetry and shape of the hydrophobic surfaces of membrane proteins play an important role in the regulation of protein function by bilayer membranes.
Highlights
The biological function of membrane proteins is determined by a complex interplay between protein structure and the properties of the surrounding lipid bilayer [1,2,3,4,5,6]
The biological function of mechanosensitive channels relies on an interplay between bilayer mechanical properties and protein structure
We predict that distinct oligomeric states and hydrophobic shapes of mechanosensitive channels lead to distinct functional responses to membrane tension
Summary
The biological function of membrane proteins is determined by a complex interplay between protein structure and the properties of the surrounding lipid bilayer [1,2,3,4,5,6]. The energetic cost of proteininduced membrane deformations depends on the protein conformational state as well as on the bilayer material properties, which allows [11,12,13,14,15,16,17] the lipid bilayer to act as a regulator of protein function. A widely-studied model system for the coupling between membrane protein function and the elastic deformation of lipid bilayers is provided by mechanosensitive ion channels. Mechanosensitive channels are capable of transducing membrane tension into an electrochemical response [21,22,23] by switching from a closed to an open conformational state with increasing membrane tension, allowing cells to sense touch, sound, and pressure
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
