Crystal structure of the pestivirus envelope glycoprotein E(rns) and mechanistic analysis of its ribonuclease activity

Structure
Thomas KreyFélix A Rey

Abstract

Pestiviruses, which belong to the Flaviviridae family of RNA viruses, are important agents of veterinary diseases causing substantial economical losses in animal farming worldwide. Pestivirus particles display three envelope glycoproteins at their surface: E(rns), E1, and E2. We report here the crystal structure of the catalytic domain of E(rns), the ribonucleolytic activity of which is believed to counteract the innate immunity of the host. The structure reveals a three-dimensional fold corresponding to T2 ribonucleases from plants and fungi. Cocrystallization experiments with mono- and oligonucleotides revealed the structural basis for substrate recognition at two binding sites previously identified for T2 RNases. A detailed analysis of poly-U cleavage products using (31)P-NMR and size exclusion chromatography, together with molecular docking studies, provides a comprehensive mechanistic picture of E(rns) activity on its substrates and reveals the presence of at least one additional nucleotide binding site.

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Citations

Mar 30, 2016·Cytokine & Growth Factor Reviews·Carmela Lussi, Matthias Schweizer
Dec 15, 2015·Frontiers in Veterinary Science·Artur Summerfield, Nicolas Ruggli
Dec 17, 2014·Virus Research·Wei JiCheng-Qiang He
Oct 23, 2009·Veterinary Microbiology·Ernst Peterhans, Matthias Schweizer
Feb 6, 2015·Journal of Virology·M Alejandra TortoriciFélix A Rey
Feb 26, 2016·Canadian Journal of Microbiology·Yan LiMingwang Zhang
Nov 2, 2018·PLoS Pathogens·Amir SaberiAlexander E Gorbalenya
Aug 30, 2019·Journal of Virology·Tomokazu TamuraYoshiharu Matsuura
Mar 16, 2017·Scientific Reports·Christiane RiedelTill Rümenapf
May 31, 2018·Scientific Reports·Carmela LussiMatthias Schweizer
May 1, 2021·Viruses·Christiane RiedelTill Rümenapf
Jun 1, 2021·Frontiers in Veterinary Science·Anwar A G Al-KubatiMaged Gomaa Hemida
Jun 1, 2021·Veterinary Microbiology·Tatsuya NishiTakehisa Yamamoto
Jul 3, 2021·Viruses·Birke Andrea TewsGregor Meyers

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