Structural basis for the geometry-driven localization of a small protein

Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):E1908-15. doi: 10.1073/pnas.1423868112. Epub 2015 Mar 30.


In bacteria, certain shape-sensing proteins localize to differently curved membranes. During sporulation in Bacillus subtilis, the only convex (positively curved) surface in the cell is the forespore, an approximately spherical internal organelle. Previously, we demonstrated that SpoVM localizes to the forespore by preferentially adsorbing onto slightly convex membranes. Here, we used NMR and molecular dynamics simulations of SpoVM and a localization mutant (SpoVM(P9A)) to reveal that SpoVM's atypical amphipathic α-helix inserts deeply into the membrane and interacts extensively with acyl chains to sense packing differences in differently curved membranes. Based on binding to spherical supported lipid bilayers and Monte Carlo simulations, we hypothesize that SpoVM's membrane insertion, along with potential cooperative interactions with other SpoVM molecules in the lipid bilayer, drives its preferential localization onto slightly convex membranes. Such a mechanism, which is distinct from that used by high curvature-sensing proteins, may be widely conserved for the localization of proteins onto the surface of cellular organelles.

Keywords: ArfGAP1; DivIVA; SpoIVA; curvature sensing; lipid packing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lipid Bilayers / metabolism
  • Magnetic Resonance Spectroscopy
  • Microscopy, Fluorescence
  • Molecular Dynamics Simulation
  • Monte Carlo Method
  • Mutation
  • Protein Binding
  • Protein Structure, Secondary*


  • Bacterial Proteins
  • Lipid Bilayers
  • spoVM protein, Bacillus subtilis
  • Green Fluorescent Proteins

Associated data

  • PDB/2MVH
  • PDB/2MVJ