title: Virus maturation targets the protein capsid to concerted disassembly and unfolding.
abstract: Many animal viruses undergo post-assembly proteolytic cleavage that is required for infectivity. The role of maturation cleavage on Flock House virus was evaluated by comparing wild type (wt) and cleavage-defective mutant (D75N) Flock House virus virus-like particles. A concerted dissociation and unfolding of the mature wt particle was observed under treatment by urea, whereas the cleavage-defective mutant dissociated to folded subunits as determined by steady-state and dynamic fluorescence spectroscopy, circular dichroism, and nuclear magnetic resonance. The folded D75N alpha subunit could reassemble into capsids, whereas the yield of reassembly from unfolded cleaved wt subunits was very low. Overall, our results demonstrate that the maturation/cleavage process targets the particle for an "off pathway" disassembly, because dissociation is coupled to unfolding. The increased motions in the cleaved capsid, revealed by fluorescence and NMR, and the concerted nature of dissociation/unfolding may be crucial to make the mature particle infectious.
authors.affiliation: Departamento de Bioquimica Médica, Instituto de Ciências Biomédicas, Centro Nacional de Ressonância Magnética Nuclear de Macromoléculas, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Oliveira
authors.forename: A M
authors.initials: AM
authors.lastname: Gomes
authors.forename: F C
authors.initials: FC
authors.lastname: Almeida
authors.forename: R
authors.initials: R
authors.lastname: Mohana-Borges
authors.forename: A P
authors.initials: AP
authors.lastname: Valente
authors.forename: V S
authors.initials: VS
authors.lastname: Reddy
authors.forename: J E
authors.initials: JE
authors.lastname: Johnson
authors.forename: J L
authors.initials: JL
authors.lastname: Silva
mesh_terms: D000818:Animals; D016367:Baculoviridae; D002213:Capsid / Q000737:chemistry*; D002850:Chromatography, Gel; D002942:Circular Dichroism; D004330:Drosophila; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009154:Mutation; D011312:Pressure; D017510:Protein Folding; D012328:RNA Viruses / Q000737:chemistry* / Q000235:genetics; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014508:Urea / Q000494:pharmacology
chemical_list: D014508:Urea