Foot-and-Mouth Disease Virus Leader Proteinase

The leader proteinase (Lpro) of foot-and-mouth disease virus frees itself from the nascent polyprotein, cleaving between its own C terminus and the N terminus of VP4 at the sequence Lys-Leu-Lys-↓-Gly-Ala-Gly. Subsequently, the Lpro impairs protein synthesis from capped mRNAs in the infected cell by processing a host protein, eukaryotic initiation factor 4GI, at the sequence Asn-Leu-Gly-↓-Arg-Thr-Thr. A rabbit reticulocyte lysate system was used to examine the substrate specificity of Lpro and the relationship of the two cleavage reactions. We show that Lpro requires a basic residue at one side of the scissile bond to carry out efficient self-processing. This reaction is abrogated when leucine and lysine prior to the cleavage site are substituted by serine and glutamine, respectively. However, the cleavage of eIF4GI is unaffected by the inhibition of self-processing. Removal of the 18-amino acid C-terminal extension of Lpro slowed eIF4GI cleavage; replacement of the C-terminal extension by unrelated amino acid sequences further delayed this cleavage. Surprisingly, wild-type Lpro and the C-terminal variants all processed the polyprotein cleavage site in an intermolecular reaction at the same rate. However, when the polyprotein cleavage site was part of the same polypeptide chain as the wild-type Lbpro, the rate of processing was much more rapid. These experiments strongly suggest that self-processing is an intramolecular reaction.

• Publication year

  2001

• Venue

  Journal of Biological Chemistry

• Publication date

  2001-09-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M104192200PMID 11459842
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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