Exploring the membrane fusion mechanism through force-induced disassembly of HIV-1 six-helix bundle

Biochem Biophys Res Commun. 2016 May 13;473(4):1185-1190. doi: 10.1016/j.bbrc.2016.04.037. Epub 2016 Apr 11.

Abstract

Enveloped virus, such as HIV-1, employs membrane fusion mechanism to invade into host cell. HIV-1 gp41 ectodomain uses six-helix bundle configuration to accomplish this process. Using molecular dynamic simulations, we confirmed the stability of this six-helix bundle by showing high occupancy of hydrogen bonds and hydrophobic interactions. Key residues and interactions important for the bundle integration were characterized by force-induced unfolding simulations of six-helix bundle, exhibiting the collapse order of these groups of interactions. Moreover, our results in some way concerted with a previous theory that the formation of coiled-coil choose a route which involved cooperative interactions between the N-terminal and C-terminal helix.

Keywords: Interfacial interaction; Membrane fusion; Molecular dynamics simulations; Protein unfolding; Six-helix bundle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / physiology*
  • HIV Envelope Protein gp41 / ultrastructure*
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Mechanotransduction, Cellular / physiology
  • Membrane Fluidity / physiology
  • Membrane Fusion / physiology*
  • Micromanipulation / methods
  • Models, Biological*
  • Molecular Dynamics Simulation*
  • Protein Conformation
  • Protein Folding
  • Protein Subunits
  • Stress, Mechanical
  • Structure-Activity Relationship

Substances

  • HIV Envelope Protein gp41
  • Protein Subunits
  • gp41 protein, Human immunodeficiency virus 1