Structural changes of envelope proteins during alphavirus fusion

Long Li, Joyce Jose, Ye Xiang, Richard J. Kuhn, Michael G. Rossmann

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Alphaviruses are enveloped RNA viruses that have a diameter of about 700Å and can be lethal human pathogens. 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 surface, 60 with quasi-three-fold symmetry and 20 coincident with the icosahedral three-fold axes arranged with T = 4 quasi-symmetry. The E1 glycoprotein has a hydrophobic fusion loop at one end and is responsible for membrane fusion. The E2 protein is responsible for receptor binding 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 cytoplasm. 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.

Original languageEnglish (US)
Pages (from-to)705-708
Number of pages4
JournalNature
Volume468
Issue number7324
DOIs
StatePublished - Dec 2 2010

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Alphavirus
Virus Internalization
Glycoproteins
Proteins
Viruses
Membrane Fusion
Viral Genome
Endosomes
RNA Viruses
Endocytosis
Virion
Immunoglobulins
Cytoplasm
Membranes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Li, L., Jose, J., Xiang, Y., Kuhn, R. J., & Rossmann, M. G. (2010). Structural changes of envelope proteins during alphavirus fusion. Nature, 468(7324), 705-708. https://doi.org/10.1038/nature09546
Li, Long ; Jose, Joyce ; Xiang, Ye ; Kuhn, Richard J. ; Rossmann, Michael G. / Structural changes of envelope proteins during alphavirus fusion. In: Nature. 2010 ; Vol. 468, No. 7324. pp. 705-708.
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Li, L, Jose, J, Xiang, Y, Kuhn, RJ & Rossmann, MG 2010, 'Structural changes of envelope proteins during alphavirus fusion', Nature, vol. 468, no. 7324, pp. 705-708. https://doi.org/10.1038/nature09546

Structural changes of envelope proteins during alphavirus fusion. / Li, Long; Jose, Joyce; Xiang, Ye; Kuhn, Richard J.; Rossmann, Michael G.

In: Nature, Vol. 468, No. 7324, 02.12.2010, p. 705-708.

Research output: Contribution to journalArticle

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