A membrane topology model for human interferon inducible transmembrane protein 1.

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 e...

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Main Authors: Stuart Weston, Stephanie Czieso, Ian J White, Sarah E Smith, Paul Kellam, Mark Marsh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0104341
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author Stuart Weston
Stephanie Czieso
Ian J White
Sarah E Smith
Paul Kellam
Mark Marsh
author_facet Stuart Weston
Stephanie Czieso
Ian J White
Sarah E Smith
Paul Kellam
Mark Marsh
author_sort Stuart Weston
collection DOAJ
description 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.
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spelling doaj-art-4d5de7daf58b49f2a0e598791beb500a2025-08-20T02:22:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10434110.1371/journal.pone.0104341A membrane topology model for human interferon inducible transmembrane protein 1.Stuart WestonStephanie CziesoIan J WhiteSarah E SmithPaul KellamMark MarshInterFeron 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.https://doi.org/10.1371/journal.pone.0104341
spellingShingle Stuart Weston
Stephanie Czieso
Ian J White
Sarah E Smith
Paul Kellam
Mark Marsh
A membrane topology model for human interferon inducible transmembrane protein 1.
PLoS ONE
title A membrane topology model for human interferon inducible transmembrane protein 1.
title_full A membrane topology model for human interferon inducible transmembrane protein 1.
title_fullStr A membrane topology model for human interferon inducible transmembrane protein 1.
title_full_unstemmed A membrane topology model for human interferon inducible transmembrane protein 1.
title_short A membrane topology model for human interferon inducible transmembrane protein 1.
title_sort membrane topology model for human interferon inducible transmembrane protein 1
url https://doi.org/10.1371/journal.pone.0104341
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