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Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children and infants. To date, there is no effective vaccine available against RSV. Heparan sulfate is a type of glycosaminoglycan that aids in the attachment of the RSV to the host cell membrane via the G...

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Detalles Bibliográficos
Autores principales: Hamza, Abu, Samad, Abdus, Parray, Zahoor Ahmad, Ara, Sajda, Ahmed, Anwar, Almajhdi, Fahad N., Hussain, Tajamul, Islam, Asimul, Parveen, Shama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880246/
https://www.ncbi.nlm.nih.gov/pubmed/35216066
http://dx.doi.org/10.3390/ijms23041950
Descripción
Sumario:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children and infants. To date, there is no effective vaccine available against RSV. Heparan sulfate is a type of glycosaminoglycan that aids in the attachment of the RSV to the host cell membrane via the G protein. In the present study, the effect of amino acid substitution on the structure and stability of the ectodomain G protein was studied. Further, it was investigated whether mutation (K117A) in the CX3C motif of G protein alters the binding with heparan sulfate. The point mutation significantly affects the conformational stability of the G protein. The mutant protein showed a low binding affinity with heparan sulfate as compared to the wild-type G protein, as determined by fluorescence quenching, isothermal titration calorimetry (ITC), and molecular docking studies. The low binding affinity and decreased stability suggested that this mutation may play an important role in prevention of attachment of virion to the host cell receptors. Collectively, this investigation suggests that mutation in the CX3C motif of G protein may likely improve the efficacy and safety of the RSV vaccine.