Membrane binding by the endophilin N-BAR domain.

Area of Science:

• Biophysics
• Molecular Biology
• Structural Biology

Background:

• Endophilin N-terminal amphipathic helix Bin/Amphiphysin/Rvs-homology (N-BAR) domains possess a unique structure with an additional insert helix.
• The precise structure and function of this insert helix remain unclear due to limitations in crystallographic studies.

Purpose of the Study:

• To investigate the interaction of endophilin N-BAR domains with lipid bilayers using molecular dynamics simulations.
• To elucidate the role of the additional insert helix in membrane bending and curvature generation.

Main Methods:

• Large-scale molecular-dynamics simulations of a single endophilin N-BAR domain interacting with a lipid bilayer.
• Modeling various configurations of the insert helix to assess their impact on membrane bending.
• Residue-residue and residue-lipid headgroup distance analysis.

Main Results:

• The insert helix consistently maintains a perpendicular orientation to the N-BAR long axis during simulations.
• Membrane bending is directly correlated with the insert helix's orientation, with the perpendicular configuration yielding maximal curvature.
• The angle between N-BAR monomers is sensitive to the insert helix orientation.

Conclusions:

• A perpendicular orientation of the insert helix is crucial for significant membrane bending by endophilin N-BAR domains.
• The findings support a membrane sensing-binding-bending mechanism for endophilin-membrane interactions.
• Simulation results align with experimental mutation data, validating the proposed model.