Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Int J Mol Sci. 2022 Feb 9;23(4):1950. doi: 10.3390/ijms23041950.
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.
呼吸道合胞病毒（RSV）是导致儿童和婴儿下呼吸道感染的主要原因。迄今为止，尚无针对 RSV 的有效疫苗。硫酸乙酰肝素是一种糖胺聚糖，通过 G 蛋白帮助 RSV 附着到宿主细胞膜上。在本研究中，研究了氨基酸取代对 G 蛋白外域结构和稳定性的影响。此外，还研究了 G 蛋白 CX3C 基序中的突变（K117A）是否改变与硫酸乙酰肝素的结合。与野生型 G 蛋白相比，点突变显著影响 G 蛋白的构象稳定性。荧光猝灭、等温滴定量热法（ITC）和分子对接研究表明，突变蛋白与硫酸乙酰肝素的结合亲和力较低。低结合亲和力和稳定性降低表明，这种突变可能在阻止病毒颗粒与宿主细胞受体结合方面发挥重要作用。总的来说，这项研究表明，G 蛋白 CX3C 基序中的突变可能提高 RSV 疫苗的疗效和安全性。
