Plasticity of influenza haemagglutinin fusion peptides and their interaction with lipid bilayers.
A detailed molecular dynamics study of the haemagglutinin fusion peptide (N-terminal 20 residues of the HA2 subunits) in a model bilayer has yielded useful information about the molecular interactions leading to insertion into the lipids. Simulations were performed on the native sequence, as well as a number of mutant sequences, which are either fusogenic or nonfusogenic. For the native sequence and fusogenic mutants, the N-terminal 11 residues of the fusion peptides are helical and insert with a tilt angle of approximately 30 degrees with respect to the membrane normal, in very good agreement with experimental data. The tilted insertion of the native sequence peptide leads to membrane bilayer thinning and the calculated order parameters show larger disorder of the alkyl chains. These results indicate that the lipid packing is perturbed by the fusion peptide and could be used to explain membrane fusion. For the nonfusogenic sequences investigated, it was found that most of them equilibrate parallel to the interface plane and do not adopt a tilted conformation. The presence of a charged residue at the beginning of the sequence (G1E mutant) resulted in a more difficult case, and the outcomes do not fall straightforwardly into the general picture. Sequence searches have revealed similarities of the fusion peptide of influenza haemagglutinin with peptide sequences such as segments of porin, amyloid alpha eta peptide, and a peptide from the prion sequence. These results confirm that the sequence can adopt different folds in different environments. The plasticity and the conformational dependence on the local environment could be used to better understand the function of fusion peptides.
National Institute for Medical Research, London, United Kingdom.
Loredana
L
Vaccaro
Karen J
KJ
Cross
Jens
J
Kleinjung
Suzana K
SK
Straus
David J
DJ
Thomas
Stephen A
SA
Wharton
John J
JJ
Skehel
Franca
F
Fraternali
D000595:Amino Acid Sequence; D001703:Biophysics / Q000379:methods*; D002244:Carbon / Q000737:chemistry; D003198:Computer Simulation; D006389:Hemagglutinins, Viral / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008561:Membrane Fusion; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D013997:Time Factors; D014764:Viral Proteins / Q000737:chemistry*
D006389:Hemagglutinins, Viral; D008051:Lipid Bilayers; D008823:Micelles; D010455:Peptides; D014764:Viral Proteins; C458881:hemagglutinin fusogenic peptide, influenza virus; D002244:Carbon