Conformational changes during proteolytic processing of a picornavirus capsid proteins

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Picornaviruses are a significant group of human and animal pathogens.
• Understanding viral protein maturation is crucial for developing antiviral strategies.
• The cleavage cascade of viral polyproteins leads to functional protein formation.

Purpose of the Study:

• To investigate conformational changes during picornavirus capsid protein processing.
• To characterize the folding properties of intermediate cleavage fragments.
• To assess the impact of distant proteolytic cleavages on protein conformation.

Main Methods:

• Utilized synthetic peptide antibodies for probing protein structures.
• Analyzed conformational differences using antibody recognition assays.
• Studied the cleavage cascade of the viral polyprotein precursor.

Main Results:

• Identified a 63 kDa fragment with distinct folding characteristics compared to its precursor and products.
• Demonstrated that proteolytic cleavages up to 520 residues away can cause significant conformational changes.
• Observed that these conformational changes render epitopes unrecognizable by antibodies.

Conclusions:

• Picornavirus polyprotein processing involves substantial conformational rearrangements.
• Proteolytic cleavage sites distant from epitopes can profoundly influence protein structure.
• This study provides the first evidence of such extensive conformational changes in the picornavirus system.