title: Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3.
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.
authors.affiliation: Hefei National Laboratory of Microscale Physical Sciences, School of Life Science, University of Science and Technology of China, Hefei, 230027, P. R. China.
authors.forename: Shenglong
authors.initials: S
authors.lastname: Ling
authors.affiliation: Hefei National Laboratory of Microscale Physical Sciences, School of Life Science, University of Science and Technology of China, Hefei, 230027, P. R. China.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Hefei National Laboratory of Microscale Physical Sciences, School of Life Science, University of Science and Technology of China, Hefei, 230027, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Hefei National Laboratory of Microscale Physical Sciences, School of Life Science, University of Science and Technology of China, Hefei, 230027, P. R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Cai
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, P. R. China.
authors.forename: Fangming
authors.initials: F
authors.lastname: Wu
authors.affiliation: Hefei National Laboratory of Microscale Physical Sciences, School of Life Science, University of Science and Technology of China, Hefei, 230027, P. R. China.
authors.forename: Longhua
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Hefei National Laboratory of Microscale Physical Sciences, School of Life Science, University of Science and Technology of China, Hefei, 230027, P. R. China.|High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, P. R. China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Tian
mesh_terms: D003600:Cytosol / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry*; D008823:Micelles; D009587:Nitrogen Isotopes / Q000737:chemistry; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D016601:RNA-Binding Proteins / Q000737:chemistry*; D013113:Spin Labels; D013499:Surface Properties
chemical_list: C080082:IFITM3 protein, human; D008565:Membrane Proteins; D008823:Micelles; D009587:Nitrogen Isotopes; D016601:RNA-Binding Proteins; D013113:Spin Labels