Structure and Dynamics of Helix-0 of the N-BAR Domain in Lipid Micelles and Bilayers

• Published in: Biophysical journal 2008-11, Vol.95 (9), p.4315-4323
• Main Authors: Löw, Christian, Weininger, Ulrich, Lee, Hwankyu, Schweimer, Kristian, Neundorf, Ines, Beck-Sickinger, Annette G., Pastor, Richard W., Balbach, Jochen
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - chemistry; Adaptor Proteins, Signal Transducing - metabolism; Amides - metabolism; Binding; Curvature; Detergents; Fluid dynamics; Humans; Hydrophobic and Hydrophilic Interactions; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipids; Magnetic Resonance Spectroscopy; Mathematical analysis; Membranes; Membranes - metabolism; Micelles; Models, Molecular; Molecular biology; Molecular structure; Nanostructure; Nuclear Proteins - chemistry; Nuclear Proteins - metabolism; Osmosis; Peptides; Protein Structure, Secondary; Protein Structure, Tertiary; Protons; Static Electricity; Time Factors; Tumor Suppressor Proteins - chemistry; Tumor Suppressor Proteins - metabolism
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1529/biophysj.108.134155

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.