Binding mechanism of the matrix domain of HIV-1 gag on lipid membranes

Elife. 2020 Aug 18;9:e58621. doi: 10.7554/eLife.58621.

Abstract

Specific protein-lipid interactions are critical for viral assembly. We present a molecular dynamics simulation study on the binding mechanism of the membrane targeting domain of HIV-1 Gag protein. The matrix (MA) domain drives Gag onto the plasma membrane through electrostatic interactions at its highly-basic-region (HBR), located near the myristoylated (Myr) N-terminus of the protein. Our study suggests Myr insertion is involved in the sorting of membrane lipids around the protein-binding site to prepare it for viral assembly. Our realistic membrane models confirm interactions with PIP2 and PS lipids are highly favored around the HBR and are strong enough to keep the protein bound even without Myr insertion. We characterized Myr insertion events from microsecond trajectories and examined the membrane response upon initial membrane targeting by MA. Insertion events only occur with one of the membrane models, showing a combination of surface charge and internal membrane structure modulate this process.

Keywords: matrix domain of hiv-1; membrane modeling; membrane targeting proteins; molecular biophysics; molecular dynamics; none; protein-lipid interactions; structural biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Membrane / metabolism*
  • HIV-1 / metabolism*
  • Membrane Lipids / metabolism*
  • Protein Binding
  • Protein Domains
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Membrane Lipids
  • gag Gene Products, Human Immunodeficiency Virus