TY - JOUR
T1 - How to lose a kink and gain a helix
T2 - PH independent conformational changes of the fusion domains from influenza hemagglutinin in heterogeneous lipid bilayers
AU - Jang, Hyunbum
AU - Michaud-Agrawal, Naveen
AU - Johnston, Jennifer M.
AU - Woolf, Thomas B.
PY - 2008/7
Y1 - 2008/7
N2 - We have simulated two conformations of the fusion domain of influenza hemagglutinin (HA) within explicit water, salt, and heterogeneous lipid bilayers composed of POPC:POPG (4:1). Each conformation has seven different starting points in which the initial peptide structure is the same for each conformation, but the location across the membrane normal and lipid arrangement around the peptide are varied, giving a combined total simulation time of 140 ns. For the HA5 conformation (primary structure from recent NMR spectroscopy at pH = 5), the peptide exhibits a stable and less kinked structure in the lipid bilayer compared to that from the NMR studies. The relative fusogenic behavior of the different conformations has been investigated by calculation of the relative free energy of insertion into the hydrophobic region of lipid bilayer as a function of the depth of immersion. For the HA7 conformations (primary structure from recent NMR spectroscopy at pH = 7.4), while the N-terminal helix preserves its initial structure, the flexible C-terminal chain produces a transient helical motif inside the lipid bilayer. This conformational change is pH-independent, and is closely related to the peptide insertion into the lipid bilayer.
AB - We have simulated two conformations of the fusion domain of influenza hemagglutinin (HA) within explicit water, salt, and heterogeneous lipid bilayers composed of POPC:POPG (4:1). Each conformation has seven different starting points in which the initial peptide structure is the same for each conformation, but the location across the membrane normal and lipid arrangement around the peptide are varied, giving a combined total simulation time of 140 ns. For the HA5 conformation (primary structure from recent NMR spectroscopy at pH = 5), the peptide exhibits a stable and less kinked structure in the lipid bilayer compared to that from the NMR studies. The relative fusogenic behavior of the different conformations has been investigated by calculation of the relative free energy of insertion into the hydrophobic region of lipid bilayer as a function of the depth of immersion. For the HA7 conformations (primary structure from recent NMR spectroscopy at pH = 7.4), while the N-terminal helix preserves its initial structure, the flexible C-terminal chain produces a transient helical motif inside the lipid bilayer. This conformational change is pH-independent, and is closely related to the peptide insertion into the lipid bilayer.
KW - Conformational change
KW - Folding in lipid bilayers
KW - Influenza fusion peptide
KW - Lipid-protein interactions
KW - Mixed lipid bilayer
KW - Thermodynamics of membrane fusion
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U2 - 10.1002/prot.21925
DO - 10.1002/prot.21925
M3 - Article
C2 - 18214961
AN - SCOPUS:44949233215
SN - 0887-3585
VL - 72
SP - 299
EP - 312
JO - Proteins: Structure, Function and Genetics
JF - Proteins: Structure, Function and Genetics
IS - 1
ER -