tetano
Editor, Senior Moderator
J Am Chem Soc. 2015 Jun 3. [Epub ahead of print]
[h=1]Closed and semi-closed interhelical structures in membrane vs closed and open structures in detergent for the influenza virus hemagglutinin fusion peptide and correlation of hydrophobic surface area with fusion catalysis.[/h] Ghosh U, Xie L, Jia L, Liang S, Weliky DP.
[h=3]Abstract[/h] The ~25 N-terminal "HAfp" residues of the HA2 subunit of the influenza virus hemagglutinin protein are critical for fusion between the viral and endosomal membranes at low pH. Earlier studies of HAfp in detergent support (1) N-helix/turn/C-helix structure at pH 5 with open interhelical geometry and N-helix/turn/C-coil structure at pH 7; or (2) N-helix/turn/C-helix at both pHs with closed interhelical geometry. These different structures led to very different models of HAfp membrane location and different models of catalysis of membrane fusion by HAfp. In this study, the inter-helical geometry of membrane-associated HAfp is probed by solid-state NMR. The data are well-fitted to a population mixture of closed and semi-closed structures. The two structures have similar interhelical geometries and are planar with hydrophobic and hydrophilic faces. The different structures of HAfp in detergent and membrane could be due to the differences in interaction with the curved micelle and flat membrane with better geometric matching between the closed and semi-closed structures and the membrane. The higher fusogenicity of longer sequences and low pH is correlated with hydrophobic surface area and consequent increased membrane perturbation.
PMID: 26039158 [PubMed - as supplied by publisher]
[h=1]Closed and semi-closed interhelical structures in membrane vs closed and open structures in detergent for the influenza virus hemagglutinin fusion peptide and correlation of hydrophobic surface area with fusion catalysis.[/h] Ghosh U, Xie L, Jia L, Liang S, Weliky DP.
[h=3]Abstract[/h] The ~25 N-terminal "HAfp" residues of the HA2 subunit of the influenza virus hemagglutinin protein are critical for fusion between the viral and endosomal membranes at low pH. Earlier studies of HAfp in detergent support (1) N-helix/turn/C-helix structure at pH 5 with open interhelical geometry and N-helix/turn/C-coil structure at pH 7; or (2) N-helix/turn/C-helix at both pHs with closed interhelical geometry. These different structures led to very different models of HAfp membrane location and different models of catalysis of membrane fusion by HAfp. In this study, the inter-helical geometry of membrane-associated HAfp is probed by solid-state NMR. The data are well-fitted to a population mixture of closed and semi-closed structures. The two structures have similar interhelical geometries and are planar with hydrophobic and hydrophilic faces. The different structures of HAfp in detergent and membrane could be due to the differences in interaction with the curved micelle and flat membrane with better geometric matching between the closed and semi-closed structures and the membrane. The higher fusogenicity of longer sequences and low pH is correlated with hydrophobic surface area and consequent increased membrane perturbation.
PMID: 26039158 [PubMed - as supplied by publisher]