title: Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1α.
abstract: The foot-and-mouth disease virus leader proteinase (Lb(pro)) cleaves itself off the nascent viral polyprotein. NMR studies on the monomeric variant Lb(pro) L200F provide structural evidence for intramolecular self-processing. (15)N-HSQC measurements of Lb(pro) L200F showed specifically shifted backbone signals in the active and substrate binding sites compared to the monomeric variant sLb(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(pro), stably binds its own CTE. Parts of the β-sheet domains but none of the α-helical domains of Lb(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(pro).
authors.affiliation: Max F. Perutz Laboratories, Medical University of Vienna, Department of Medical Biochemistry, Dr. Bohr-Gasse 9/3, A-1030 Vienna, Austria.
authors.forename: Jutta
authors.initials: J
authors.lastname: Steinberger
authors.forename: Georg
authors.initials: G
authors.lastname: Kontaxis
authors.forename: Chiara
authors.initials: C
authors.lastname: Rancan
authors.forename: Tim
authors.initials: T
authors.lastname: Skern
mesh_terms: D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029544:Foot-and-Mouth Disease Virus / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D019316:Porcine respiratory and reproductive syndrome virus / Q000201:enzymology* / Q000235:genetics; D017510:Protein Folding; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D017361:Viral Nonstructural Proteins; D010450:Endopeptidases; C088747:leader proteinase, foot-and-mouth disease virus
keywords: Active site; C-terminal extension; CTE; FMDV; Foot-and-mouth disease virus; Lb(pro); Leader proteinase; Non-structural protein; PRRSV; Papain-like cysteine proteinase; Polyprotein processing; Porcine reproductive and respiratory syndrome virus; Protein fold; Shortened leader proteinase (lacking 6 C-terminal amino acids); Substrate binding; Wildtype; nsp; sLb(pro); wt