How to lose a kink and gain a helix

PH independent conformational changes of the fusion domains from influenza hemagglutinin in heterogeneous lipid bilayers

Hyunbum Jang, Naveen Michaud-Agrawal, Jennifer M. Johnston, Thomas B Woolf

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)299-312
Number of pages14
JournalProteins
Volume72
Issue number1
DOIs
StatePublished - Jul 2008

Fingerprint

Lipid bilayers
Hemagglutinins
Lipid Bilayers
Human Influenza
Conformations
Fusion reactions
Peptides
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance spectroscopy
Immersion
Membrane Lipids
Saline water
Salts
Free energy
Nuclear magnetic resonance
Water
Membranes
Lipids

Keywords

  • Conformational change
  • Folding in lipid bilayers
  • Influenza fusion peptide
  • Lipid-protein interactions
  • Mixed lipid bilayer
  • Thermodynamics of membrane fusion

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry

Cite this

How to lose a kink and gain a helix : PH independent conformational changes of the fusion domains from influenza hemagglutinin in heterogeneous lipid bilayers. / Jang, Hyunbum; Michaud-Agrawal, Naveen; Johnston, Jennifer M.; Woolf, Thomas B.

In: Proteins, Vol. 72, No. 1, 07.2008, p. 299-312.

Research output: Contribution to journalArticle

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