Engineering de novo membrane-mediated protein-protein communication networks

J Am Chem Soc. 2012 Apr 4;134(13):5746-9. doi: 10.1021/ja300523q. Epub 2012 Mar 26.

Abstract

Mechanical properties of biological membranes are known to regulate membrane protein function. Despite this, current models of protein communication typically feature only direct protein-protein or protein-small molecule interactions. Here we show for the first time that, by harnessing nanoscale mechanical energy within biological membranes, it is possible to promote controlled communication between proteins. By coupling lipid-protein modules and matching their response to the mechanical properties of the membrane, we have shown that the action of phospholipase A(2) on acyl-based phospholipids triggers the opening of the mechanosensitive channel, MscL, by generating membrane asymmetry. Our findings confirm that the global physical properties of biological membranes can act as information pathways between proteins, a novel mechanism of membrane-mediated protein-protein communication that has important implications for (i) the underlying structure of signaling pathways, (ii) our understanding of in vivo communication networks, and (iii) the generation of building blocks for artificial protein networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena
  • Cell Membrane / metabolism*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Genetic Engineering / methods*
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Lipid Bilayers / metabolism
  • Phospholipases A2, Secretory / metabolism*
  • Phospholipids / metabolism
  • Protein Binding

Substances

  • Escherichia coli Proteins
  • Ion Channels
  • Lipid Bilayers
  • MscL protein, E coli
  • Phospholipids
  • Phospholipases A2, Secretory