Structure and dynamics of helix-0 of the N-BAR domain in lipid micelles and bilayers

Biophys J. 2008 Nov 1;95(9):4315-23. doi: 10.1529/biophysj.108.134155. Epub 2008 Jul 25.

Abstract

Bin/Amphiphysin/Rvs-homology (BAR) domains generate and sense membrane curvature by binding the negatively charged membrane to their positively charged concave surfaces. N-BAR domains contain an N-terminal extension (helix-0) predicted to form an amphipathic helix upon membrane binding. We determined the NMR structure and nano-to-picosecond dynamics of helix-0 of the human Bin1/Amphiphysin II BAR domain in sodium dodecyl sulfate and dodecylphosphocholine micelles. Molecular dynamics simulations of this 34-amino acid peptide revealed electrostatic and hydrophobic interactions with the detergent molecules that induce helical structure formation from residues 8-10 toward the C-terminus. The orientation in the micelles was experimentally confirmed by backbone amide proton exchange. The simulation and the experiment indicated that the N-terminal region is disordered, and the peptide curves to adopted the micelle shape. Deletion of helix-0 reduced tubulation of liposomes by the BAR domain, whereas the helix-0 peptide itself was fusogenic. These findings support models for membrane curving by BAR domains in which helix-0 increases the binding affinity to the membrane and enhances curvature generation.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amides / metabolism
  • Detergents
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Lipid Bilayers / chemistry*
  • Lipid Bilayers / metabolism*
  • Magnetic Resonance Spectroscopy
  • Membranes / metabolism
  • Micelles*
  • Models, Molecular
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protons
  • Static Electricity
  • Time Factors
  • Tumor Suppressor Proteins / chemistry*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Amides
  • BIN1 protein, human
  • Detergents
  • Lipid Bilayers
  • Micelles
  • Nuclear Proteins
  • Protons
  • Tumor Suppressor Proteins