Asymmetric genome organization in an RNA virus revealed via graph-theoretical analysis of tomographic data

PLoS Computational Biology
James A GeraetsR Twarock

Abstract

Cryo-electron microscopy permits 3-D structures of viral pathogens to be determined in remarkable detail. In particular, the protein containers encapsulating viral genomes have been determined to high resolution using symmetry averaging techniques that exploit the icosahedral architecture seen in many viruses. By contrast, structure determination of asymmetric components remains a challenge, and novel analysis methods are required to reveal such features and characterize their functional roles during infection. Motivated by the important, cooperative roles of viral genomes in the assembly of single-stranded RNA viruses, we have developed a new analysis method that reveals the asymmetric structural organization of viral genomes in proximity to the capsid in such viruses. The method uses geometric constraints on genome organization, formulated based on knowledge of icosahedrally-averaged reconstructions and the roles of the RNA-capsid protein contacts, to analyse cryo-electron tomographic data. We apply this method to the low-resolution tomographic data of a model virus and infer the unique asymmetric organization of its genome in contact with the protein shell of the capsid. This opens unprecedented opportunities to analyse vira...Continue Reading

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Citations

May 5, 2016·Bacteriophage·Peter G StockleyReidun Twarock
Mar 27, 2016·Current Opinion in Virology·Michael F Hagan, Roya Zandi
Nov 3, 2015·Acta Crystallographica. Section A, Foundations and Advances·Reidun TwarockEmilio Zappa
Apr 6, 2019·Annual Review of Biophysics·Reidun Twarock, Peter G Stockley
Apr 30, 2016·Acta Crystallographica. Section A, Foundations and Advances·A Janner
May 24, 2018·Nature Communications·Reidun TwarockPeter G Stockley

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Methods Mentioned

BETA
X-ray

Software Mentioned

UCSF Chimera SegmentMap
UCSF Chimera Segment Map
EM
stats
UCSF Chimera
STNV
scipy
Chimera

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