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Structural Changes of Envelope Proteins During Alphavirus Fusion

Alphaviruses are enveloped RNA viruses that have a diameter of about 700 Å and can be lethal human pathogens1 (Fig. 1). Entry of virus into host cells by endocytosis is controlled by two envelope glycoproteins, E1 and E2. The E2-E1 heterodimers form 80 trimeric spikes on the icosahedral virus surfac...

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Autores principales: Li, Long, Jose, Joyce, Xiang, Ye, Kuhn, Richard J., Rossmann, Michael G.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057476/
https://www.ncbi.nlm.nih.gov/pubmed/21124457
http://dx.doi.org/10.1038/nature09546
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author Li, Long
Jose, Joyce
Xiang, Ye
Kuhn, Richard J.
Rossmann, Michael G.
author_facet Li, Long
Jose, Joyce
Xiang, Ye
Kuhn, Richard J.
Rossmann, Michael G.
author_sort Li, Long
collection PubMed
description Alphaviruses are enveloped RNA viruses that have a diameter of about 700 Å and can be lethal human pathogens1 (Fig. 1). Entry of virus into host cells by endocytosis is controlled by two envelope glycoproteins, E1 and E2. The E2-E1 heterodimers form 80 trimeric spikes on the icosahedral virus surface1,2, 60 with quasi-threefold symmetry and 20 coincident with the icosahedral threefold axes arranged with T=4 quasi-symmetry (Fig. 1a). The E1 glycoprotein has a hydrophobic fusion loop at one end and is responsible for membrane fusion3,4. The E2 protein is responsible for receptor binding5,6 and protects the fusion loop at neutral pH. The lower pH in the endosome induces the virions to undergo an irreversible conformational change in which E2 and E1 dissociate and E1 forms homotrimers, triggering fusion of the viral membrane with the endosomal membrane and then releasing the viral genome into the cytoplasm3,4. Here we report the structure of an alphavirus spike, crystallized at low pH, representing an intermediate in the fusion process and clarifying the maturation process. The trimer of E2-E1 in the crystal structure is similar to the spikes in the neutral pH virus except that the E2 middle region is disordered, exposing the fusion loop. The amino- and carboxy-terminal domains of E2 each form immunoglobulin-like folds, consistent with the receptor attachment properties of E2.
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spelling pubmed-30574762011-06-02 Structural Changes of Envelope Proteins During Alphavirus Fusion Li, Long Jose, Joyce Xiang, Ye Kuhn, Richard J. Rossmann, Michael G. Nature Article Alphaviruses are enveloped RNA viruses that have a diameter of about 700 Å and can be lethal human pathogens1 (Fig. 1). Entry of virus into host cells by endocytosis is controlled by two envelope glycoproteins, E1 and E2. The E2-E1 heterodimers form 80 trimeric spikes on the icosahedral virus surface1,2, 60 with quasi-threefold symmetry and 20 coincident with the icosahedral threefold axes arranged with T=4 quasi-symmetry (Fig. 1a). The E1 glycoprotein has a hydrophobic fusion loop at one end and is responsible for membrane fusion3,4. The E2 protein is responsible for receptor binding5,6 and protects the fusion loop at neutral pH. The lower pH in the endosome induces the virions to undergo an irreversible conformational change in which E2 and E1 dissociate and E1 forms homotrimers, triggering fusion of the viral membrane with the endosomal membrane and then releasing the viral genome into the cytoplasm3,4. Here we report the structure of an alphavirus spike, crystallized at low pH, representing an intermediate in the fusion process and clarifying the maturation process. The trimer of E2-E1 in the crystal structure is similar to the spikes in the neutral pH virus except that the E2 middle region is disordered, exposing the fusion loop. The amino- and carboxy-terminal domains of E2 each form immunoglobulin-like folds, consistent with the receptor attachment properties of E2. 2010-12-02 /pmc/articles/PMC3057476/ /pubmed/21124457 http://dx.doi.org/10.1038/nature09546 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Li, Long
Jose, Joyce
Xiang, Ye
Kuhn, Richard J.
Rossmann, Michael G.
Structural Changes of Envelope Proteins During Alphavirus Fusion
title Structural Changes of Envelope Proteins During Alphavirus Fusion
title_full Structural Changes of Envelope Proteins During Alphavirus Fusion
title_fullStr Structural Changes of Envelope Proteins During Alphavirus Fusion
title_full_unstemmed Structural Changes of Envelope Proteins During Alphavirus Fusion
title_short Structural Changes of Envelope Proteins During Alphavirus Fusion
title_sort structural changes of envelope proteins during alphavirus fusion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057476/
https://www.ncbi.nlm.nih.gov/pubmed/21124457
http://dx.doi.org/10.1038/nature09546
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