Structural studies of Chikungunya virus maturation.

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TitleStructural studies of Chikungunya virus maturation.
Publication TypeJournal Article
Year of Publication2017
AuthorsYap, MLan, Klose, T, Urakami, A, S Hasan, S, Akahata, W, Rossmann, MG
JournalProc Natl Acad Sci U S A
Date Published2017 12 26
KeywordsChikungunya virus, Cryoelectron Microscopy, Glycoproteins, Protein Domains, Protein Structure, Secondary, Viral Envelope Proteins

Cleavage of the alphavirus precursor glycoprotein p62 into the E2 and E3 glycoproteins before assembly with the nucleocapsid is the key to producing fusion-competent mature spikes on alphaviruses. Here we present a cryo-EM, 6.8-Å resolution structure of an "immature" Chikungunya virus in which the cleavage site has been mutated to inhibit proteolysis. The spikes in the immature virus have a larger radius and are less compact than in the mature virus. Furthermore, domains B on the E2 glycoproteins have less freedom of movement in the immature virus, keeping the fusion loops protected under domain B. In addition, the nucleocapsid of the immature virus is more compact than in the mature virus, protecting a conserved ribosome-binding site in the capsid protein from exposure. These differences suggest that the posttranslational processing of the spikes and nucleocapsid is necessary to produce infectious virus.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID29203665
PubMed Central IDPMC5748190
Grant ListR01 AI095366 / AI / NIAID NIH HHS / United States