Picornaviruses encode their proteins in the form of a single, long, open reading frame. These polyproteins are, however, 'processed' by virus-encoded proteinases : proteolytic domains within the polyprotein. These proteinases are molecular 'mimics' of host-cell proteinases. The nascent polyproteins may be cleaved in an intramolecular reaction ('primary' cleavages in cis), or, in subsequent post-translational reactions in an intermolecular fashion ('secondary' cleavages in trans). ....... Picornavirus Polyprotein Processing

A primary cleavage between the 2A and 2B proteins of the aphtho- (foot-and-mouth disease: FMDV) and cardioviruses is mediated by 2A cleaving at it's own C-terminus. in FMDV this region is only 18aa long. This oligopeptide sequence can also mediate cleavage when included within artificial polyprotein systems comprising reporter proteins, with no othewr FMDV sequences. Recently we have shown that this 'cleavage' is not a proteolytic event, but represents an entirely novel manipulation of the translational apparatus giving rise to an apparent cleavage: actually, synthesis of two discrete products from a single open reading frame. .. 2A-Mediated Cleavage

Our model of 2A-mediated 'cleavage' involves an interaction between the nascent (hellical) 2A peptide and the exit tunnel of the ribosome: such interactions are known to bring about a 'pause' in ribosome processivity. We also postulate the interaction serves to 'fix' the turn - proposed to form the base of the 2A helix - in the peptidyl-transferase centre of the ribosome thereby altering the position of the ester bond linking the tRNA to the peptide. This 'translational' model of 2A-mediated cleavage is given in our recent publiations.

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Staff, Current Grants

Group Publications.

(Others) Published Applications of 2A.