Structure and Function of Picornavirus Proteinases

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Abstract
This chapter summarizes the implications of three-dimensional structures on the proteolytic mechanisms, the substrate specificities, and the functions of the proteinases in infected cells. The picornaviral polyproteins can be divided into three regions, designated P1, P2, and P3. These correspond to the N-terminal capsid protein precursor (P1, containing the four capsid proteins 1A-1D), the middle of the polyprotein containing three of the nonstructural proteins (P2, the three proteins 2A-2C), and the most C-terminal segment of the polyprotein containing four nonstructural proteins (P3, proteins 3A-3D). In the cardio- and aphthoviruses, a protein known as the leader protein precedes P1. The hepato- and parechoviruses encode only a single proteolytic enzyme and are therefore proteolytically the simplest of the picornaviruses. During the replication of a picornavirus, the physiology and ultrastructure of the infected cells are drastically modified. Thus, cellular RNA and protein synthesis as well as protein trafficking are inhibited. The chapter discusses crystal structures in terms of their mechanisms of action and specificities and how the proteinases have evolved to be able to carry out their specific roles in the replication of the respective viruses. Like Streptomyces griseus protease B (SGPB) and the 3C proteinases, HRV2 2Apro comprises two subdomains, built up by β-strands as found in chymotrypsin.