Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions

Parveen, Shama; Samad, Abdus; Imam, Md. Ali; Faizan, Md Imam; Ahmed, Anwar; Almajhdi, Fahad N.; Hussain, Tajamul; Islam, Asimul

doi:10.3390/molecules26237398

Cited by 6 publications

(14 citation statements)

References 72 publications

(78 reference statements)

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“…Therefore, the non-native state of the mutant G protein at pH 2.0 and 3.0 was regarded as an acid-induced molten globule like state. Similar to the mutant protein, the wild-type G protein also formed the molten globule like state at highly acidic pH values in our previous investigation [45]; in both cases, this was attributed to the hydrophobic patches being exposed when the protein was populated at pH 2.0 and 3.0 in the solutions. It was observed that the ANS fluorescence intensity decreased as the pH of the solution moved toward the basic condition (inset of Figure 4).…”

Section: Ans Binding Measurementssupporting

confidence: 61%

“…The thermodynamic stability parameters of mutant G protein are given in Table 1. In our previous investigation, we reported the GdmCl-and urea-induced denaturation of the wild-type G protein [45], in which we found that GdmCl-and urea-induced denaturation followed a two-state transition mechanism. The ∆G D 0 value of the wild-type G protein in the presence of urea was 3.76 ± 0.34 kcal mol −1 ; however, it was found to be 2.87 ± 0.21 kcal mol −1 in the mutant G protein, which indicated that the wild-type G protein was more stable than the mutant G protein in the presence of urea.…”

Section: Gdmcl-and Urea-induced Denaturationmentioning

confidence: 91%

“…The ∆G D 0 value of the wild-type G protein in the presence of urea was 3.76 ± 0.34 kcal mol −1 ; however, it was found to be 2.87 ± 0.21 kcal mol −1 in the mutant G protein, which indicated that the wild-type G protein was more stable than the mutant G protein in the presence of urea. The C m value for the mutant G protein was found to be 2.90 ± 0.13 M, while it was 4.42 ± 0.16 M in the case of the wild-type G protein [45]. It is well known that urea interacts differently with hydrophobic groups than with either protein backbones or hydrophilic groups [52].…”

Section: Gdmcl-and Urea-induced Denaturationmentioning

confidence: 91%

“…On the other hand, the ∆G D 0 value of the wild-type G protein in the presence of GdmCl was 2.53 ± 0.20 kcal mol −1 ; however, it was found to be 2.22 ± 0.22 kcal mol −1 in the mutant G protein, which we attributed to the wild-type G protein being more stable than the mutant G protein in the presence of GdmCl. The C m values of the wild-type (1.52 ± 0.07 M) and mutant protein (1.48 ± 0.08 M) were found to be similar in the presence of GdmCl; i.e., ~1.5 M [45]. The unfolding transitions induced by GdmCl and urea are not always found to be similar; the difference in the free energy of unfolding might have been due to the ionic effect of GdmCl [54].…”

Section: Gdmcl-and Urea-induced Denaturationmentioning

confidence: 93%

“…A redshift in emission maxima is indicative of the increased solvent interactions of aromatic amino acids due to the unfolding of the protein [44]. Previously, we reported that the wild-type G protein showed a redshift of 5 nm in the λ max only at pH 12.0 [45]. Finally, our fluorescence study concluded that the tertiary structure of the protein was perturbed as we moved from the physiological pH to the acidic or basic pH values, and changes in the λ max were observed in highly basic and acidic pH conditions.…”

Section: Cloning Expression and Purification Of The Mutant G Proteinmentioning

confidence: 94%

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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

Parveen

Samad

Parray

et al. 2022

IJMS

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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.

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Section: Ans Binding Measurementssupporting

confidence: 61%

Section: Gdmcl-and Urea-induced Denaturationmentioning

confidence: 91%

Section: Gdmcl-and Urea-induced Denaturationmentioning

confidence: 91%

Section: Gdmcl-and Urea-induced Denaturationmentioning

confidence: 93%

Section: Cloning Expression and Purification Of The Mutant G Proteinmentioning

confidence: 94%

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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

Parveen

Samad

Parray

et al. 2022

IJMS

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Some new insights into the biological activities of carboxymethylated polysaccharides from Lasiodiplodia theobromae

Pires,

de Gois Andriolo,

Lopes

et al. 2023

BMC Complement Med Ther

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Background Carboxymethylated Lasiodiplodan (LaEPS-C), Lasiodiplodia theobromae β-glucan exopolysaccharide derivative, has a well-known range of biological activities. Compared to LaEPS-C, its fractions, Linear (LLaEPS-C) and Branched (BLaEPS-C), have biological potentialities scarcely described in the literature. So, in this study, we investigate the immunomodulatory, antiviral, antiproliferative, and anticoagulant activities of LLaEPS-C and BLaEPS-C and compare them to the LaEPS-C. Methods LaEPS was obtained from L. theobromae MMBJ. After carboxymethylation, LaEPS-C structural characteristics were confirmed by Elementary Composition Analysis by Energy Dispersive X-Ray Detector (EDS), Fourier Transform Infrared (FTIR), and Nuclear Magnetic Resonance (NMR). The immunomodulatory activity on cytokine secretion was evaluated in human monocyte-derived macrophage cultures. The antiviral activity was evaluated by Hep-2 cell viability in the presence or absence of hRSV (human respiratory syncytial virus). In vitro antiproliferative activity was tested by sulforhodamine B assay. The anticoagulant activity was determined by APTT (Activated Partial Thromboplastin Time) and PT (Prothrombin Time). Results LaEPS-C showed low macrophage cell viability only at 100 µg/mL (52.84 ± 24.06, 48 h), and LLaEPS-C presented no effect. Conversely, BLaEPS-C showed cytotoxicity from 25 to 100 µg/mL (44.36 ± 20.16, 40.64 ± 25.55, 33.87 ± 25.16; 48 h). LaEPS-C and LLaEPS-C showed anti-inflammatory activity. LaEPS-C presented this at 100 µg/mL (36.75 ± 5.53, 48 h) for IL-10, and LLaEPS-C reduces TNF-α cytokine productions at 100 µg/mL (18.27 ± 5.80, 48 h). LLaEPS-C showed an anti-hRSV activity (0.7 µg/ml) plus a low cytotoxic activity for Hep-2 cells (1.4 µg/ml). LaEPS-C presented an antiproliferative activity for NCI-ADR/RES (GI50 65.3 µg/mL). A better PT was achieved for LLaEPS-C at 5.0 µg/mL (11.85 ± 0.87s). Conclusions These findings demonstrated that carboxymethylation effectively improves the biological potential of the LaEPS-C and their fractions. From those polysaccharides tested, LLaEPS provided the best results with low toxicity for anti-inflammatory, antiviral, and anticoagulant activities.

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Molecular docking and dynamics simulation studies uncover the host-pathogen protein-protein interactions in Penaeus vannamei and Vibrio parahaemolyticus

Rosilan,

Jamali,

Sufira

et al. 2024

PLoS ONE

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Shrimp aquaculture contributes significantly to global economic growth, and the whiteleg shrimp, Penaeus vannamei, is a leading species in this industry. However, Vibrio parahaemolyticus infection poses a major challenge in ensuring the success of P. vannamei aquaculture. Despite its significance in this industry, the biological knowledge of its pathogenesis remains unclear. Hence, this study was conducted to identify the interaction sites and binding affinity between several immune-related proteins of P. vannamei with V. parahaemolyticus proteins associated with virulence factors. Potential interaction sites and the binding affinity between host and pathogen proteins were identified using molecular docking and dynamics (MD) simulation. The P. vannamei-V. parahaemolyticus protein-protein interaction of Complex 1 (Ferritin-HrpE/YscL family type III secretion apparatus protein), Complex 2 (Protein kinase domain-containing protein-Chemotaxis CheY protein), and Complex 3 (GPCR-Chemotaxis CheY protein) was found to interact with -4319.76, -5271.39, and -4725.57 of the docked score and the formation of intermolecular bonds at several interacting residues. The docked scores of Complex 1, Complex 2, and Complex 3 were validated using MD simulation analysis, which revealed these complexes greatly contribute to the interactions between P. vannamei and V. parahaemolyticus proteins, with binding free energies of -22.50 kJ/mol, -30.20 kJ/mol, and -26.27 kJ/mol, respectively. This finding illustrates the capability of computational approaches to search for molecular binding sites between host and pathogen, which could increase the knowledge of Vibrio spp. infection on shrimps, which then can be used to assist in the development of effective treatment.

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Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions

Cited by 6 publications

References 72 publications

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

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

Some new insights into the biological activities of carboxymethylated polysaccharides from Lasiodiplodia theobromae

Molecular docking and dynamics simulation studies uncover the host-pathogen protein-protein interactions in Penaeus vannamei and Vibrio parahaemolyticus

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