Identification of a Pocket Factor That is Critical to Zika Virus Assembly

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Oct 3

PMID 33009400

Citations 19

Authors

Nadia M DiNunno

Daniel J Goetschius

Anoop Narayanan

Sydney A Majowicz

Ibrahim Moustafa

Carol M Bator

Susan L Hafenstein

Joyce Jose

Affiliations

Soon will be listed here.

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 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.

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