Structural modeling and analysis of dengue-mediated inhibition of interferon signaling pathway
| Autor: | Samar H. K. Tareen, Rehan Zafar Paracha, Umar Niazi, Syed Aun Muhammad, Shah Khusro, Jamil Ahmad, Babar Aslam, Azevedo, Amjad Ali, T Ahmad |
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| Přispěvatelé: | RS: FSE MaCSBio, RS: FPN MaCSBio |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Ubiquitin-Protein Ligases viruses Static Electricity Alpha interferon SIAH2 Viral Nonstructural Proteins Dengue virus medicine.disease_cause Protein Structure Secondary Dengue fever Dengue Ubiquitin Interferon Genetics medicine Humans Amino Acid Sequence Protein Interaction Maps STAT2 Molecular Biology biology Ubiquitination Nuclear Proteins virus diseases STAT2 Transcription Factor General Medicine Dengue Virus medicine.disease Virology Molecular Docking Simulation STAT1 Transcription Factor Interferon Type I biology.protein STAT protein Hydrophobic and Hydrophilic Interactions Sequence Alignment Signal Transduction medicine.drug |
| Zdroj: | Genetics and molecular research : GMR, 14(2), 4215-4237. Fundacao de Pesquisas Cientificas de Ribeirao Preto |
| ISSN: | 1676-5680 |
| Popis: | Dengue virus (DENV) belongs to the family Flaviviridae and can cause major health problems worldwide, including dengue fever and dengue shock syndrome. DENV replicon in human cells inhibits interferon alpha and beta with the help of its non-structural proteins. Non-structural protein 5 (NS5) of DENV is responsible for the proteasome-mediated degradation of signal transducer and activator of transcription (STAT) 2 protein, which has been implicated in the development of resistance against interferon-mediated antiviral effect. This degradation of STAT2 primarily occurs with the help of E3 ubiquitin ligases. Seven in absentia homologue (SIAH) 2 is a host protein that can mediate the ubiquitination of proteins and is known for its interaction with NS5. In this study, comprehensive computational analysis was performed to characterize the protein-protein interactions between NS5, SIAH2, and STAT2 to gain insight into the residues and sites of interaction between these proteins. The objective of the study was to structurally characterize the NS5-STAT2, SIAH2-STAT2, and NS5-SIAH2 interactions along with the determination of the possible reaction pattern for the degradation of STAT2. Docking and physicochemical studies indicated that DENV NS5 may first interact with the host SIAH2, which can then proceed towards binding with STAT2 from the side of SIAH2. These implications are reported for the first time and require validation by wet-lab studies. |
| Databáze: | OpenAIRE |
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