Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3

Sci Rep. 2016 Apr 5;6:24029. doi: 10.1038/srep24029.

Abstract

Interferon-inducible transmembrane protein IFITM3 was known to restrict the entry of a wide spectrum of viruses to the cytosol of the host. The mechanism used by the protein to restrict viral entry is unclear given the unavailability of the membrane topology and structures of the IFITM family proteins. Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Solution NMR studies of the same sample verified the secondary structure distribution and demonstrated two rigid regions interacting with the micellar surface. The resulting membrane topology of IFITM3 supports the mechanism of an enhanced restricted membrane hemi-fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytosol / metabolism
  • Electron Spin Resonance Spectroscopy*
  • Humans
  • Magnetic Resonance Spectroscopy*
  • Membrane Fusion
  • Membrane Proteins / chemistry*
  • Micelles
  • Nitrogen Isotopes / chemistry
  • Protein Domains
  • Protein Structure, Secondary
  • RNA-Binding Proteins / chemistry*
  • Spin Labels
  • Surface Properties

Substances

  • IFITM3 protein, human
  • Membrane Proteins
  • Micelles
  • Nitrogen Isotopes
  • RNA-Binding Proteins
  • Spin Labels