Journal: Nat Commun / Year: 2020 Title: Identification of a pocket factor that is critical to Zika virus assembly. Authors: Nadia M DiNunno / Daniel J Goetschius / Anoop Narayanan / Sydney A Majowicz / Ibrahim Moustafa / Carol M Bator / Susan L Hafenstein / Joyce Jose / Abstract: Zika virus (ZIKV) is an emerging mosquito borne flavivirus and a major public health concern causing severe disease. Due to the presence of a lipid membrane and structural heterogeneity, attaining an ...Zika virus (ZIKV) is an emerging mosquito borne flavivirus and a major public health concern causing severe disease. Due to the presence of a lipid membrane and structural heterogeneity, attaining an atomic resolution structure is challenging, but important to understand virus assembly and life cycle mechanisms that offer distinct targets for therapeutic intervention. We here use subvolume refinement to achieve a 3.4 Å resolution structure and identify two distinct lipid moieties. The first arises from the inner leaflet and is coordinated by hydrophobic residues of the M and E transmembrane helices that form a binding pocket not previously characterized. The second lipid arises from the outer leaflet coordinate between two E protein helices. Structure-based mutagenesis identifies critical hydrophobic interactions and their effect on the virus life cycle. Results show that lipids play an essential role in the ZIKV assembly pathway revealing a potential target of lipid based antiviral drug development.
History
Deposition
Aug 30, 2020
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Header (metadata) release
Sep 16, 2020
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Map release
Sep 16, 2020
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Update
Oct 14, 2020
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Current status
Oct 14, 2020
Processing site: RCSB / Status: Released
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