Background: Binding appropriate cellular receptors is a crucial step of a lifecycle for any virus. Structure of receptor-binding domain for a viral surface protein has to be determined before the start of future drug design projects.
Objective: Investigation of pH-induced changes in the secondary structure for a capsid peptide with loss of function mutation can shed some light on the mechanism of entrance.
Methods: Spectroscopic methods were accompanied by electrophoresis, ultrafiltration, and computational biochemistry.
Results: In this study, we showed that a peptide from the receptor-binding domain of Parvovirus B19 VP1 capsid (residues 13-31) is beta-structural at pH=7.4 in 0.01 M phosphate buffer, but alpha- helical at pH=5.0, according to the circular dichroism (CD) spectroscopy results. Results of infra- red (IR) spectroscopy showed that the same peptide exists in both alpha-helical and beta-structural conformations in partial dehydration conditions both at pH=7.4 and pH=5.0. In contrast, the peptide with Y20W mutation, which is known to block the internalization of the virus, forms mostly alpha-helical conformation in partial dehydration conditions at pH=7.4. According to our hypothesis, an intermolecular antiparallel beta structure formed by the wild-type peptide in its tetramers at pH=7.4 is the prototype of the similar intermolecular antiparallel beta structure formed by the corresponding part of Parvovirus B19 receptor-binding domain with its cellular receptor (AXL).
Conclusion: Loss of function Y20W substitution in VP1 capsid protein prevents the shift into the beta-structural state by way of alpha helix stabilization and the decrease of its ability to turn into the disordered state.
Keywords: parvovirus B19; sheet to helix transition; capsid protein; synthetic peptide; receptor-binding domainparvovirus B19; sheet to helix transition; capsid protein; synthetic peptide; receptor-binding domain.
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