title: Structure and dynamics of helix-0 of the N-BAR domain in lipid micelles and bilayers.
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.
authors.affiliation: Institut für Physik, Biophysik, Martin-Luther-Universität Halle-Wittenberg, D-06120 Halle (Saale), Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Löw
authors.forename: Ulrich
authors.initials: U
authors.lastname: Weininger
authors.forename: Hwankyu
authors.initials: H
authors.lastname: Lee
authors.forename: Kristian
authors.initials: K
authors.lastname: Schweimer
authors.forename: Ines
authors.initials: I
authors.lastname: Neundorf
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
authors.forename: Richard W
authors.initials: RW
authors.lastname: Pastor
authors.forename: Jochen
authors.initials: J
authors.lastname: Balbach
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000577:Amides / Q000378:metabolism; D003902:Detergents; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008566:Membranes / Q000378:metabolism; D008823:Micelles; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D055672:Static Electricity; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000577:Amides; C101410:BIN1 protein, human; D003902:Detergents; D008051:Lipid Bilayers; D008823:Micelles; D009687:Nuclear Proteins; D011522:Protons; D025521:Tumor Suppressor Proteins