Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study.
Amino Acid Substitution
/ genetics
CX3C Chemokine Receptor 1
/ genetics
Calorimetry
/ methods
Cell Line
GTP-Binding Proteins
/ genetics
Heparitin Sulfate
/ metabolism
Humans
Molecular Docking Simulation
/ methods
Mutation
/ genetics
Receptors, Chemokine
/ genetics
Respiratory Syncytial Virus Infections
/ metabolism
Respiratory Syncytial Virus, Human
/ metabolism
Spectrum Analysis
/ methods
Viral Envelope Proteins
/ genetics
Virion
/ genetics
Virus Replication
/ genetics
CX3C motif
G protein
RSV
fluorescence binding
glycosaminoglycan
heparan sulfate
isothermal titration calorimetry
molecular docking
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
09 Feb 2022
09 Feb 2022
Historique:
received:
16
12
2021
revised:
22
01
2022
accepted:
28
01
2022
entrez:
26
2
2022
pubmed:
27
2
2022
medline:
29
3
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35216066
pii: ijms23041950
doi: 10.3390/ijms23041950
pmc: PMC8880246
pii:
doi:
Substances chimiques
CX3C Chemokine Receptor 1
0
Receptors, Chemokine
0
Viral Envelope Proteins
0
Heparitin Sulfate
9050-30-0
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Council of Scientific and Industrial Research
ID : 37(1697)17/EMR-II
Organisme : Central Council for Research in Unani Medicine
ID : F.No.3-63/2019-CCRUM/Tech
Organisme : Deanship of Scientific Research at King Saud University
ID : RG-1439-74
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