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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Löw C,Weininger U,Lee H,Schweimer K,Neundorf I,Beck-Sickinger AG,Pastor RW,Balbach J

doi

10.1529/biophysj.108.134155

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

4315-23

issue

9

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(08)78570-9

journal_volume

95

pub_type

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