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Title: Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1α

The foot-and-mouth disease virus leader proteinase (Lb{sup pro}) cleaves itself off the nascent viral polyprotein. NMR studies on the monomeric variant Lb{sup pro} L200F provide structural evidence for intramolecular self-processing. {sup 15}N-HSQC measurements of Lb{sup pro} L200F showed specifically shifted backbone signals in the active and substrate binding sites compared to the monomeric variant sLb{sup pro}, lacking six C-terminal residues. This indicates transient intramolecular interactions between the C-terminal extension (CTE) of one molecule and its own active site. Contrastingly, the porcine reproductive and respiratory syndrome virus (PRRSV) leader proteinase nsp1α, with a papain-like fold like Lb{sup pro}, stably binds its own CTE. Parts of the β-sheet domains but none of the α-helical domains of Lb{sup pro} and nsp1α superimpose; consequently, the α-helical domain of nsp1α is oriented differently relative to its β-sheet domain. This provides a large interaction surface for the CTE with the globular domain, stabilising the intramolecular complex. Consequently, self-processing inactivates nsp1α but not Lb{sup pro}. - Highlights: • We examine self-processing of the leader protease of foot-and-mouth disease virus. • NMR analysis strongly supports intramolecular self-processing. • Self-processing is a dynamic process with no stable complex. • Structural comparison with nsp1α of PRRSV which forms stable intramolecularmore » complex. • Subdomain orientation explains differences in stability of intramolecular complexes.« less
Authors:
 [1] ;  [2] ;  [3] ;  [1]
  1. Max F. Perutz Laboratories, Medical University of Vienna, Department of Medical Biochemistry, Dr. Bohr-Gasse 9/3, A-1030 Vienna (Austria)
  2. Max F. Perutz Laboratories, University of Vienna, Department of Structural and Computational Biology, Campus Vienna Biocenter 5, A-1030 Vienna (Austria)
  3. Helmholtz Zentrum München, Department of Gene Vectors, Haematologikum, Marchioninistrasse 25, D-81377 Munich (Germany)
Publication Date:
OSTI Identifier:
22436637
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 443; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; COMPARATIVE EVALUATIONS; COMPLEXES; DISEASES; FEET; INTERACTIONS; NITROGEN 15; NUCLEAR MAGNETIC RESONANCE; ORAL CAVITY; PAPAIN; PROCESSING; SUBSTRATES; SURFACES; VIRUSES