Structural view of the 2A protease from human rhinovirus C15

The majority of outbreaks of the common cold are caused by rhinoviruses. The 2A protease (2A^pro) of human rhinoviruses (HRVs) is known to play important roles in the propagation of the virus and the modulation of host signal pathways to facilitate viral replication. The 2A^pro from human rhinovirus C15 (HRV-C15) has been expressed in Escherichia coli and purified by affinity chromatography, ion-exchange chromatography and gel-filtration chromatography. The crystals diffracted to 2.6 Å resolution. The structure was solved by molecular replacement using the structure of 2A^pro from coxsackievirus A16 (CVA16) as the search model. The structure contains a conserved His–Asp–Cys catalytic triad and a Zn²⁺-binding site. Comparison with other 2A^pro structures from enteroviruses reveals that the substrate-binding cleft of 2A^pro from HRV-C15 exhibits a more open conformation, which presumably favours substrate binding.