Abstract
The global burden of disease caused by a respiratory syncytial virus (RSV) is becoming more widely recognized in young children and adults. Heparan sulfate helps in attaching the virion through G protein with the host cell membrane. In this study, we examined the structural changes of ectodomain G protein (edG) in a wide pH range. The absorbance results revealed that protein maintains its tertiary structure at physiological and highly acidic and alkaline pH. However, visible aggregation of protein was observed in mild acidic pH. The intrinsic fluorescence study shows no significant change in the λmax except at pH 12.0. The ANS fluorescence of edG at pH 2.0 and 3.0 forms an acid-induced molten globule-like state. The denaturation transition curve monitored by fluorescence spectroscopy revealed that urea and GdmCl induced denaturation native (N) ↔ denatured (D) state follows a two-state process. The fluorescence quenching, molecular docking, and 50 ns simulation measurements suggested that heparan sulfate showed excellent binding affinity to edG. Our binding study provides a preliminary insight into the interaction of edG to the host cell membrane via heparan sulfate. This binding can be inhibited using experimental approaches at the molecular level leading to the prevention of effective host–pathogen interaction.
Highlights
Introduction iationsRespiratory syncytial virus (RSV) is a lower respiratory tract pathogen that causes pneumonia and bronchiolitis in children, especially those younger than five years of age
The G protein of respiratory syncytial virus (RSV) plays a vital role in the host–pathogen interaction, which is mediated by pH-dependent or independent pathways [30,32]
#K calculated from fluorescence quenching, *∆G calculated from molecular docking, @K calculated from isothermal titration calorimetry (ITC), *Kd calculated from microscale thermophoresis (MST)
Summary
The G protein of RSV plays a vital role in the host–pathogen interaction, which is mediated by pH-dependent or independent pathways [30,32]. The role of G protein is very crucial for attachment to the host cell receptors. Since all the biological processes are controlled by the pH of the environments, it eventually determines its stability. We performed the pH-based and chemical-induced denaturation study to examine its effect on the structural and conformational stability of edG in in vitro conditions. We determined the binding interaction studies of heparan sulfate with edG by fluorescence quenching and in silico approaches
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
