Crystal Structure of the Pestivirus Envelope Glycoprotein Erns and Mechanistic Analysis of Its Ribonuclease Activity

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 crysta...

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Bibliographic Details
Published in:Structure (London) 2012-05, Vol.20 (5), p.862-873
Main Authors: Krey, Thomas, Bontems, Francois, Vonrhein, Clemens, Vaney, Marie-Christine, Bricogne, Gerard, Rümenapf, Till, Rey, Félix A.
Format: Article
Language:English
Subjects:
Binding sites
Crystal structure
Diseases
Economics
Envelopes
Flaviviridae
Glycoprotein
Molecular structure
Pestivirus
Three dimensional
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Summary: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. ► First pestivirus envelope glycoprotein structure ► Confirmation of evolutionary link with RNases of plants and fungi ► Evidence for a third nucleotide binding site in a T2 RNase ► Nonprocessive mechanism of polynucleotide degradation
ISSN:0969-2126
1878-4186
DOI:10.1016/j.str.2012.03.018