Membrane pore formation at protein-lipid interfaces

Trends Biochem Sci. 2014 Nov;39(11):510-6. doi: 10.1016/j.tibs.2014.09.002. Epub 2014 Oct 19.


Pore-forming proteins (PFPs) interact with lipid bilayers to compromise membrane integrity. Many PFPs function by inserting a ring of oligomerized subunits into the bilayer to form a protein-lined hydrophilic channel. However, mounting evidence suggests that PFPs can also generate 'proteolipidic' pores by contributing to the fusion of inner and outer bilayer leaflets to form a toroidal structure. We discuss here toroidal pore formation by peptides including melittin, protegrin, and Alzheimer's Aβ1-41, as well as by PFPs from several evolutionarily unrelated families: the colicin/Bcl-2 grouping including the pro-apoptotic protein Bax, actinoporins derived from sea anemones, and the membrane attack complex-perforin/cholesterol dependent cytolysin (MACPF/CDC) set of proteins. We also explore how the structure and biological role of toroidal pores might be investigated further.

Keywords: Bcl-2/colicin family proteins; MACPF/CDC family proteins; actinoporins; pore-forming peptides and proteins; protein–membrane interactions; toroidal pore formation.

Publication types

  • Review

MeSH terms

  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism
  • Colicins / chemistry
  • Colicins / metabolism
  • Lipid Bilayers / chemistry*
  • Lipid Bilayers / metabolism
  • Melitten / chemistry
  • Melitten / metabolism
  • Membrane Lipids / chemistry*
  • Membrane Lipids / metabolism
  • Models, Molecular
  • Pore Forming Cytotoxic Proteins / chemistry*
  • Pore Forming Cytotoxic Proteins / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary


  • Colicins
  • Lipid Bilayers
  • Membrane Lipids
  • Pore Forming Cytotoxic Proteins
  • Melitten