Cooperative Gating and Spatial Organization of Membrane Proteins through Elastic Interactions

Abstract

Biological membranes are elastic media in which the presence of a transmembrane protein leads to local bilayer deformation. The energetics of deformation allow two membrane proteins in close proximity to influence each other's equilibrium conformation via their local deformations, and spatially organize the proteins based on their geometry. We use the mechanosensitive channel of large conductance (MscL) as a case study to examine the implications of bilayer-mediated elastic interactions on protein conformational statistics and clustering. The deformations around MscL cost energy on the order of 10 kT and extend ~3nm from the protein edge, as such elastic forces induce cooperative gating and we propose experiments to measure these effects. Additionally, since elastic interactions are coupled to protein conformation, we find that conformational changes can severely alter the average separation between two proteins. This has important implications for how conformational changes organize membrane proteins into functional groups within membranes.

12 pages, 6 figures, 63 references, submitted to PLoS Computational Biology

References in corpus (6)

• Membrane-protein interactions in mechanosensitive channels
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• Interactions between proteins bound to biomembranes
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• Bilayer-thickness-mediated interactions between integral membrane proteins
• Polar Chemoreceptor Clustering by Coupled Trimers of Dimers
• Architecture and Function of Mechanosensitive Membrane Protein Lattices
• Composition variation and underdamped mechanics near membrane proteins and coats
• Signatures of protein structure in the cooperative gating of mechanosensitive ion channels
• Collective response of self-organised clusters of mechanosensitive channels
• Membrane-mediated interactions
• Controlling the shape of membrane protein polyhedra
• Dependence of protein-induced lipid bilayer deformations on protein shape
• Cooperative response and clustering: consequences of membrane-mediated interactions among mechanosensitive channels
• Thermodynamic competition between membrane protein oligomeric states
• Biological Extension of the Action Principle: Endpoint Determination beyond the Quantum Level and the Ultimate Physical Roots of Consciousness