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| Subject Categories: Microbiology & Pathogens | Membranes & Transport |
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| The EMBO Journal
(2004) 23, 54–65, doi:10.1038/sj.emboj.7600012 Published online 11 December 2003 |
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| Isomerization of the intersubunit disulphide-bond in Env controls retrovirus fusion |
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| Michael Wallin, Maria Ekström and Henrik Garoff |
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Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden To whom correspondence should be addressed Henrik Garoff, Molecular Biology Laboratory, Center of Biotechnology, Novum, S-141 57 Huddinge, Sweden. Tel.: +46 8 6089125; Fax: +46 8 7745538; E-mail: henrik.garoff@cbt.ki.se Received 5 August 2003; Accepted 15 October 2003; Published online 11 December 2003. |
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| Abstract |
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| The membrane fusion activity of murine leukaemia virus Env is carried by the transmembrane (TM) and controlled by the peripheral (SU) subunit. We show here that all Env subunits of the virus form disulphide-linked SU–TM complexes that can be disrupted by treatment with NP-40, heat or urea, or by Ca2+ depletion. Thiol mapping indicated that these conditions induced isomerization of the disulphide-bond by activating a thiol group in a Cys-X-X-Cys (CXXC) motif in SU. This resulted in dissociation of SU from the virus. The active thiol was hidden in uninduced virus but became accessible for alkylation by either Ca2+ depletion or receptor binding. The alkylation inhibited isomerization, virus fusion and infection. DTT treatment of alkylated Env resulted in cleavage of the SU–TM disulphide-bond and rescue of virus fusion. Further studies showed that virus fusion was specifically inhibited by high and enhanced by low concentrations of Ca2+. These results suggest that Env is stabilized by Ca2+ and that receptor binding triggers a cascade of reactions involving Ca2+ removal, CXXC-thiol exposure, SU–TM disulphide-bond isomerization and SU dissociation, which lead to fusion activation. |
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| Keywords: disulphide-bond isomerase motif, fusion, retrovirus |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHCerebral blood flow response in adenosine 2a receptor knockout mice during transient hypoxic hypoxia Journal of Cerebral Blood Flow & Metabolism Original Article Turning of the receptor-binding domains opens up the murine leukaemia virus Env for membrane fusion The EMBO Journal Article (22 Oct 2008) A novel disulphide switch mechanism in Ero1α balances ER oxidation in human cells The EMBO Journal Article (19 Nov 2008) In vivo selection of protease cleavage sites from retrovirus display libraries Nature Biotechnology Research Article (01 Oct 1998) The EMBO Journal Article (15 Mar 1997) |
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