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Electrostatic interactions between capsid and scaffolding proteins mediate the structural polymorphism of a double-stranded RNA virus.

ABSTRACT: Capsid proteins that adopt distinct conformations constitute a paradigm of the structural polymorphism of macromolecular assemblies. We show the molecular basis of the flexibility mechanism of VP2, the capsid protein of the double-stranded RNA virus infectious bursal disease virus. The initial assembly, a procapsid-like structure, is built by the protein precursor pVP2 and requires VP3, the other infectious bursal disease virus major structural protein, which acts as a scaffold. The pVP2 C-terminal region, which is proteolyzed during virus maturation, contains an amphipathic alpha-helix that acts as a molecular switch. In the absence of VP3, efficient virus-like particle assembly occurs when the structural unit is a VP2-based chimeric protein with an N-terminal-fused His(6) tag. The His tag has a positively charged N terminus and a negatively charged C terminus, both important for virion-like structure assembly. The charge distributions of the VP3 C terminus and His tag are similar. We tested whether the His tag emulates the role of VP3 and found that the presence of a VP3 C-terminal peptide in VP2-based chimeric proteins resulted in the assembly of virus-like particles. We analyzed the electrostatic interactions between these two charged morphogenetic peptides, in which a single residue was mutated to impede the predicted interaction, followed by a compensatory double mutation to rescue electrostatic interactions. The effects of these mutations were monitored by following the virus-like and/or virus-related assemblies. Our results suggest that the basic face of the pVP2 amphipathic alpha-helix interacts with the acidic region of the VP3 C terminus and that this interaction is essential for VP2 acquisition of competent conformations for capsid assembly.

SUBMITTER: Saugar I

PROVIDER: S-EPMC2823505 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Electrostatic interactions between capsid and scaffolding proteins mediate the structural polymorphism of a double-stranded RNA virus.

Saugar Irene I Irigoyen Nerea N Luque Daniel D Carrascosa José L JL Rodríguez José F JF Castón José R JR

The Journal of biological chemistry 20091120 6

Capsid proteins that adopt distinct conformations constitute a paradigm of the structural polymorphism of macromolecular assemblies. We show the molecular basis of the flexibility mechanism of VP2, the capsid protein of the double-stranded RNA virus infectious bursal disease virus. The initial assembly, a procapsid-like structure, is built by the protein precursor pVP2 and requires VP3, the other infectious bursal disease virus major structural protein, which acts as a scaffold. The pVP2 C-termi ...[more]

PMID: 19933276

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Electrostatic interactions between capsid and scaffolding proteins mediate the structural polymorphism of a double-stranded RNA virus.

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Electrostatic interactions between capsid and scaffolding proteins mediate the structural polymorphism of a double-stranded RNA virus.

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