Crystal structure of the pestivirus envelope glycoprotein Erns and mechanistic analysis of its ribonuclease activity

Thomas Krey*, Francois Bontems, Clemens Vonrhein, Marie Christine Vaney, Gerard Bricogne, Till Rümenapf, Félix A. Rey

*Corresponding author for this work
36 Citations (Scopus)

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: Erns, E1, and E2. We report here the crystal structure of the catalytic domain of Erns, 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 31P-NMR and size exclusion chromatography, together with molecular docking studies, provides a comprehensive mechanistic picture of Erns activity on its substrates and reveals the presence of at least one additional nucleotide binding site.

Original languageEnglish
JournalStructure
Volume20
Issue number5
Pages (from-to)862-873
Number of pages12
ISSN0969-2126
DOIs
Publication statusPublished - 09.05.2012

Cite this