Virus maturation targets the protein capsid to concerted disassembly and unfolding

Many animal viruses undergo post-assembly proteolytic cleavage that is requ ired for infectivity, The role of maturation cleavage on Flock House virus was evaluated by comparing wild type (wt) and cleavage-defective mutant (D7 5N) Flock House virus virus-like particles. A concerted dissociation and un folding of the mature wt particle was observed under treatment by urea, whe reas the cleavage-defective mutant dissociated to folded subunits as determ ined by steady-state and dynamic fluorescence spectroscopy, circular dichro ism, and nuclear magnetic resonance. The folded D75N a subunit could reasse mble into capsids, whereas the yield of reassembly from unfolded cleaved al pha subunits was very low. Overall, our results demonstrate that the matura tion/cleavage process targets the particle for an "off pathway" disassembly , because dissociation is coupled to unfolding. The increased motions in th e cleaved capsid, revealed by fluorescence and NMR, and the concerted natur e of dissociation/unfolding may be crucial to make the mature particle infe ctious.