|Family type peptidase||N08.001 - poliovirus capsid VP0-type self-cleaving protein (human poliovirus 1), MEROPS Accession MER0172778 (peptidase unit: 2-341)|
|Content of family||Family N8 includes self-cleaving endopeptidases|
Identifier created: MEROPS 9.3 (7 September 2010)|
Picornaviruses are single-stranded RNA viruses. Processing of the viral polyprotein by picornains 3C (C03.001) and 2A (C03.020) generates capsid proteins VP0 (N08.001), VP1 and VP3, but VP0 undergoes an autolytic cleavage during virion assembly to generate capsid proteins VP2 and VP4 (Larsen et al., 1982). The autolytic cleavage was originally thought to be the action of a serine-type peptidase (Arnold et al., 1987), but from analogy with the similar autoproteolytic cleavages that are known for capsid proteins from nodaviruses (N1), tetraviruses (N2), picobirnaviruses (N5) and reoviruses (N7), it is more likely that VP0 is an asparagine-type peptidase.
|Active site residues||N,Q69 |
|Active site||Cleavage occurs at Asn69+Ser in poliovirus VP0, and this residue is assumed to be the active site nucleophile. Presumably a catalytic dyad exists with an Asp or Glu being the other component (by analogy with the nodavirus (N01.001) and tetravirus (N02.001) coat proteins). VP0 is not cleaved if His195 is mutated (Hindiyeh et al., 1999). Asn69 is replaced by Gln in some VP0 proteins from rhinovirus, and cleavage is known to occur in the coat protein from rhinovirus 16 from the solved tertiary structures (Hadfield et al., 1997). It is perhaps more probable that a Gln-Ser bond might be cleaved by picornain 3C (C03.001) than that a glutamine can act autolytically. In some enteroviruses Asn69 is replaced by Lys; cleavage of the enterovirus VP0 protein has been assumed but not demonstrated and no cleavage occurred when enterovirus 71 polyprotein was expressed in insect cells (Chung et al., 2006). Foot-and-mouth disease virus VP0 protein is also cleaved, but at an Ala+Asp bond (Curry et al., 1997), which we assume to be cleavage by a host protein.|
|Activities and specificities||The only peptidase activity is cleavage of the VP0 viral capsid protein into VP2 and VP4 in the provirion.|
|Molecular structure||Tertiary structures have been solved for several picornavirus capsids, and the structure of uncleaved VP0 has been determined from the structure of an empty poliovirus capsid. The uncleaved bond is located 20 Angstroms away from its position in the cleaved protein, and is in a trefoil-shaped depression reminiscent of an RNA binding site in bean pod mottle virus. Cleavage may therefore be RNA-dependent (Basavappa et al., 1994). The structure of VP0 resembles that of the coat proteins from nodaviruses and tetraviruses. Consequently, peptidase family N8 is included in clan NA.|