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Topology, Antiviral Functional Residues and Mechanism of IFITM1
Interferon-inducible transmembrane proteins (IFITM1/2/3) have been reported to suppress the entry of a wide range of viruses. However, their antiviral functional residues and specific mechanisms are still unclear. Here, we firstly resolved the topology of IFITM1 on the plasma membrane where N-termin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150853/ https://www.ncbi.nlm.nih.gov/pubmed/32182730 http://dx.doi.org/10.3390/v12030295 |
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author | Sun, Fang Xia, Zhiqiang Han, Yuewen Gao, Minjun Wang, Luyao Wu, Yingliang Sabatier, Jean-Marc Miao, Lixia Cao, Zhijian |
author_facet | Sun, Fang Xia, Zhiqiang Han, Yuewen Gao, Minjun Wang, Luyao Wu, Yingliang Sabatier, Jean-Marc Miao, Lixia Cao, Zhijian |
author_sort | Sun, Fang |
collection | PubMed |
description | Interferon-inducible transmembrane proteins (IFITM1/2/3) have been reported to suppress the entry of a wide range of viruses. However, their antiviral functional residues and specific mechanisms are still unclear. Here, we firstly resolved the topology of IFITM1 on the plasma membrane where N-terminus points into the cytoplasm and C-terminus resides extracellularly. Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Similarly, KRRK basic residues of IFITM2/3 also contributed to suppressing ZIKV replication. Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Overall, our study provided topology, antiviral functional residues and the mechanism of interferon-inducible transmembrane proteins. |
format | Online Article Text |
id | pubmed-7150853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71508532020-04-20 Topology, Antiviral Functional Residues and Mechanism of IFITM1 Sun, Fang Xia, Zhiqiang Han, Yuewen Gao, Minjun Wang, Luyao Wu, Yingliang Sabatier, Jean-Marc Miao, Lixia Cao, Zhijian Viruses Article Interferon-inducible transmembrane proteins (IFITM1/2/3) have been reported to suppress the entry of a wide range of viruses. However, their antiviral functional residues and specific mechanisms are still unclear. Here, we firstly resolved the topology of IFITM1 on the plasma membrane where N-terminus points into the cytoplasm and C-terminus resides extracellularly. Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Similarly, KRRK basic residues of IFITM2/3 also contributed to suppressing ZIKV replication. Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Overall, our study provided topology, antiviral functional residues and the mechanism of interferon-inducible transmembrane proteins. MDPI 2020-03-08 /pmc/articles/PMC7150853/ /pubmed/32182730 http://dx.doi.org/10.3390/v12030295 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sun, Fang Xia, Zhiqiang Han, Yuewen Gao, Minjun Wang, Luyao Wu, Yingliang Sabatier, Jean-Marc Miao, Lixia Cao, Zhijian Topology, Antiviral Functional Residues and Mechanism of IFITM1 |
title | Topology, Antiviral Functional Residues and Mechanism of IFITM1 |
title_full | Topology, Antiviral Functional Residues and Mechanism of IFITM1 |
title_fullStr | Topology, Antiviral Functional Residues and Mechanism of IFITM1 |
title_full_unstemmed | Topology, Antiviral Functional Residues and Mechanism of IFITM1 |
title_short | Topology, Antiviral Functional Residues and Mechanism of IFITM1 |
title_sort | topology, antiviral functional residues and mechanism of ifitm1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150853/ https://www.ncbi.nlm.nih.gov/pubmed/32182730 http://dx.doi.org/10.3390/v12030295 |
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