Architecture and Function of Mechanosensitive Membrane Protein Lattices

TL;DR

This study reveals how bilayer-mediated elastic interactions influence the formation and architecture of membrane protein lattices, linking protein symmetry to collective function.

Contribution

It demonstrates that membrane elastic interactions can produce specific lattice architectures and connect protein symmetry with collective membrane protein functions.

Findings

Membrane elastic interactions can organize proteins into regular lattices.

Different protein symmetries lead to distinct lattice architectures.

Lattice architecture influences activation barriers and function.

Abstract

Experiments have revealed that membrane proteins can form two-dimensional clusters with regular translational and orientational protein arrangements, which may allow cells to modulate protein function. However, the physical mechanisms yielding supramolecular organization and collective function of membrane proteins remain largely unknown. Here we show that bilayer-mediated elastic interactions between membrane proteins can yield regular and distinctive lattice architectures of protein clusters, and may provide a link between lattice architecture and lattice function. Using the mechanosensitive channel of large conductance (MscL) as a model system, we obtain relations between the shape of MscL and the supramolecular architecture of MscL lattices. We predict that the tetrameric and pentameric MscL symmetries observed in previous structural studies yield distinct lattice architectures of MscL clusters and that, in turn, these distinct MscL lattice architectures yield distinct lattice activation barriers. Our results suggest general physical mechanisms linking protein symmetry, the lattice architecture of membrane protein clusters, and the collective function of membrane protein lattices.