title: A membrane topology model for human interferon inducible transmembrane protein 1.
abstract: InterFeron Inducible TransMembrane proteins 1-3 (IFITM1, IFITM2 and IFITM3) are a family of proteins capable of inhibiting the cellular entry of numerous human and animal viruses. IFITM1-3 are unique amongst the currently described viral restriction factors in their apparent ability to block viral entry. This restrictive property is dependant on the localisation of the proteins to plasma and endosomal membranes, which constitute the main portals of viral entry into cells. The topology of the IFITM proteins within cell membranes is an unresolved aspect of their biology. Here we present data from immunofluorescence microscopy, protease cleavage, biotin-labelling and immuno-electron microscopy assays, showing that human IFITM1 has a membrane topology in which the N-terminal domain resides in the cytoplasm, and the C-terminal domain is extracellular. Furthermore, we provide evidence that this topology is conserved for all of the human interferon-induced IFITM proteins. This model is consistent with that recently proposed for murine IFITM3, but differs from that proposed for murine IFITM1.
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Weston
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Czieso
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: White
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Smith
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom; MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Kellam
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom; MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Marsh
mesh_terms: D000943:Antigens, Differentiation / Q000737:chemistry* / Q000648:ultrastructure*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D011487:Protein Conformation; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000943:Antigens, Differentiation; D017931:DNA Primers; C062010:leu-13 antigen
references.citation: PLoS Pathog. 2011 Jan 06;7(1):e1001258
references.pmid: 21253575
references.citation: J Virol. 2013 Sep;87(17):9923-7
references.pmid: 23804635
references.citation: Nature. 2012 Mar 25;484(7395):519-23
references.pmid: 22446628
references.citation: J Virol. 2012 Dec;86(24):13697-707
references.pmid: 23055554
references.citation: J Virol. 2013 Dec;87(23):12957-66
references.pmid: 24067955
references.citation: Blood. 1990 Dec 15;76(12):2583-93
references.pmid: 2265250
references.citation: PLoS Pathog. 2014 Apr 03;10(4):e1004048
references.pmid: 24699674
references.citation: Cell Rep. 2013 Nov 27;5(4):895-908
references.pmid: 24268777
references.citation: PLoS Pathog. 2013 Jan;9(1):e1003124
references.pmid: 23358889
references.citation: Cell. 2009 Dec 24;139(7):1243-54
references.pmid: 20064371
references.citation: J Microsc. 2006 Dec;224(Pt 3):213-32
references.pmid: 17210054
references.citation: Curr Opin Virol. 2014 Feb;4:71-7
references.pmid: 24480526
references.citation: J Virol. 2013 Jul;87(14):7837-52
references.pmid: 23658454
references.citation: PLoS Pathog. 2012 Sep;8(9):e1002909
references.pmid: 22969429
references.citation: PLoS Pathog. 2011 Oct;7(10):e1002337
references.pmid: 22046135
references.citation: Cell Host Microbe. 2013 Apr 17;13(4):452-64
references.pmid: 23601107
references.citation: Nat Chem Biol. 2010 Aug;6(8):610-4
references.pmid: 20601941
references.citation: J Biol Chem. 2013 Nov 8;288(45):32184-32193
references.pmid: 24067232
references.citation: J Biol Chem. 2012 Jun 1;287(23):19631-41
references.pmid: 22511783
references.citation: J Immunol. 1990 Oct 1;145(7):2207-13
references.pmid: 2398277
references.citation: Eur J Biochem. 1991 Jul 15;199(2):417-23
references.pmid: 1906403
references.citation: Proc Natl Acad Sci U S A. 2014 May 6;111(18):6756-61
references.pmid: 24753610
references.citation: J Cell Biol. 2007 Apr 23;177(2):329-41
references.pmid: 17438075
references.citation: Cell. 1984 Oct;38(3):745-55
references.pmid: 6548414
references.citation: PLoS One. 2014 May 14;9(5):e96579
references.pmid: 24827144
references.citation: J Cell Biol. 1991 Apr;113(1):123-35
references.pmid: 2007617
references.citation: J Immunol. 1984 Nov;133(5):2496-501
references.pmid: 6332852
references.citation: Cell Microbiol. 2014 Jul;16(7):1080-93
references.pmid: 24521078