Key result
The Lpro L143A variant efficiently self-processed at cleavage sites containing P2 phenylalanine, demonstrating that residue L143 is a key determinant of FMDV leader proteinase cleavage specificity.
Residue L143 of the FMDV leader proteinase is a key determinant of its restricted cleavage specificity, specifically excluding substrates with phenylalanine at the P2 position.
The foot-and-mouth disease virus (FMDV) leader proteinase (L(pro)) self-processes inefficiently at the L(pro)/VP4 cleavage site LysLeuLys*GlyAlaGly (* indicates cleaved peptide bond) when the leucine at position P2 is replaced by phenylalanine. Molecular modeling and energy minimization identified the L(pro) residue L143 as being responsible for this discrimination. The variant L(pro) L143A self-processed efficiently at the L(pro)/VP4 cleavage site containing P2 phenylalanine, whereas the L143M variant did not. L(pro) L143A self-processing at the eIF4GII sequence AspPheGly*ArgGlnThr was improved but showed more-extensive aberrant processing. Residue 143 in L(pro) is occupied only by leucine and methionine in all sequenced FMDV serotypes, implying that these bulky side chains are one determinant of the restricted specificity of L(pro).
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Mayer et al. (2008) studied Foot-and-Mouth Disease Virus (FMDV) infection (in vitro model). Lpro L143A mutation vs. Wild-type Lpro and L143M variant was evaluated on Self-processing efficiency at the Lpro/VP4 cleavage site containing P2 phenylalanine. The Lpro L143A variant efficiently self-processed at cleavage sites containing P2 phenylalanine, demonstrating that residue L143 is a key determinant of FMDV leader proteinase cleavage specificity.
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