ROLE AND MECHANISM OF THE MATURATION CLEAVAGE OF VPO IN POLIOVIRUS ASSEMBLY - STRUCTURE OF THE EMPTY CAPSID ASSEMBLY INTERMEDIATE AT 2.9-ANGSTROM RESOLUTION

The crystal structure of the P1/Mahoney poliovirus empty capsid has be en determined at 2.9 Angstrom resolution. The empty capsids differ fro m mature virions in that they lack the viral RNA and have yet to under go a stabilizing maturation cleavage of VP0 to yield the mature capsid proteins VP4 and VP2. The outer surface and the bulk of the protein s hell are very similar to those of the mature virion. The major differe nces between the 2 structures are focused in a network formed by the N -terminal extensions of the capsid proteins on the inner surface of th e shell. In the empty capsids, the entire N-terminal extension of VP1, as well as portions corresponding to VP4 and the N-terminal extension of VP2, are disordered, and many stabilizing interactions that are pr esent in the mature virion are missing. In the empty capsid, the VP0 s cissile bond is located some 20 Angstrom away from the positions in th e mature virion of the termini generated by VP0 cleavage. The scissile bond is located on the rim of a trefoil-shaped depression in the inne r surface of the shell that is highly reminiscent of an RNA binding si te in bean pod mottle virus. The structure suggests plausible (and ult imately testable) models for the initiation of encapsidation, for the RNA-dependent autocatalytic cleavage of VP0, and for the role of the c leavage in establishing the ordered N-terminaI network and in generati ng stable virions.