D155Y substitution of SARS-CoV-2 ORF3a weakens binding with Caveolin-1
| Autor: | Suchetana Gupta, Ditipriya Mallick, Kumarjeet Banerjee, Shrimon Mukherjee, Soumyadev Sarkar, Sonny TM Lee, Partha Basuchowdhuri, Siddhartha S Jana |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Cryo-EM
Cryo Electron Microscope In silico ORF3a RMSD Root Mean Square Deviation Mutant Biophysics Virulence Biochemistry Interactome Article MMGBSA Molecular mechanics with generalized Born and surface area solvation BLAST Basic Local Alignment Search Tool NF-κB Nuclear factor kappa light chain enhancer of activated B cells ORF Open Reading Frame PROVEAN Protein Variation Effect Analyzer Caveolin-1 Structural Biology PDB Protein Data Bank Molecular dynamics simulation Genetics ASC Apoptosis associated speck-like protein containing a caspase recruitment domain CD4+ Cluster of Differentiation 4+ ComputingMethodologies_COMPUTERGRAPHICS HMOX1 Heme Oxygenase 1 TRIM59 Tripartite motif-containing protein 59 chemistry.chemical_classification SUN2 SUN domain-containing protein 2 Chemistry SARS-CoV-2 PISA Protein Interfaces Surfaces and Assemblies ARL6IP6 ADP Ribosylation Factor Like GTPase 6 interacting protein 6 MERS-CoV Middle East respiratory syndrome coronavirus NLRP3 Nucleotide-binding oligomerization domain Leucine rich repeat and Pyrin domain containing NCBI National Centre for Biotechnology Information Computer Science Applications IFN Interferon Amino acid Graph theory Docking (molecular) COVID-19 Coronavirus Disease 2019 Caveolin 1 Mutation CD8+ Cluster of Differentiation 8+ Salt bridge TP248.13-248.65 Biotechnology |
| Zdroj: | Computational and Structural Biotechnology Journal, Vol 20, Iss, Pp 766-778 (2022) Computational and Structural Biotechnology Journal |
| ISSN: | 2001-0370 |
| Popis: | Graphical abstract The clinical manifestation of the recent pandemic COVID-19, caused by the novel SARS-CoV-2 virus, varies from mild to severe respiratory illness. Although environmental, demographic and co-morbidity factors have an impact on the severity of the disease, contribution of the mutations in each of the viral genes towards the degree of severity needs a deeper understanding for designing a better therapeutic approach against COVID-19. Open Reading Frame-3a (ORF3a) protein has been found to be mutated at several positions. In this work, we have studied the effect of one of the most frequently occurring mutants, D155Y of ORF3a protein, found in Indian COVID-19 patients. Using computational simulations we demonstrated that the substitution at 155th changed the amino acids involved in salt bridge formation, hydrogen-bond occupancy, interactome clusters, and the stability of the protein compared with the other substitutions found in Indian patients. Protein–protein docking using HADDOCK analysis revealed that substitution D155Y weakened the binding affinity of ORF3a with caveolin-1 compared with the other substitutions, suggesting its importance in the overall stability of ORF3a-caveolin-1 complex, which may modulate the virulence property of SARS-CoV-2. |
| Databáze: | OpenAIRE |
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