The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid
The assembly of picornavirus capsids proceeds through the stepwise oligomerization of capsid protein subunits and depends on interactions between critical residues known as hotspots. Few studies have described the identification of hotspot residues at the protein subunit interfaces of the picornavir...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/12/4/387 |
| _version_ | 1797571817501622272 |
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| author | Nicole Upfold Caroline Ross Özlem Tastan Bishop Caroline Knox |
| author_facet | Nicole Upfold Caroline Ross Özlem Tastan Bishop Caroline Knox |
| author_sort | Nicole Upfold |
| collection | DOAJ |
| description | The assembly of picornavirus capsids proceeds through the stepwise oligomerization of capsid protein subunits and depends on interactions between critical residues known as hotspots. Few studies have described the identification of hotspot residues at the protein subunit interfaces of the picornavirus capsid, some of which could represent novel drug targets. Using a combination of accessible web servers for hotspot prediction, we performed a comprehensive bioinformatic analysis of the hotspot residues at the intraprotomer, interprotomer and interpentamer interfaces of the Theiler’s murine encephalomyelitis virus (TMEV) capsid. Significantly, many of the predicted hotspot residues were found to be conserved in representative viruses from different genera, suggesting that the molecular determinants of capsid assembly are conserved across the family. The analysis presented here can be applied to any icosahedral structure and provides a platform for in vitro mutagenesis studies to further investigate the significance of these hotspots in critical stages of the virus life cycle with a view to identify potential targets for antiviral drug design. |
| first_indexed | 2024-03-10T20:46:56Z |
| format | Article |
| id | doaj.art-7f82440f9065420aade926eff9226908 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T20:46:56Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-7f82440f9065420aade926eff92269082023-11-19T20:16:28ZengMDPI AGViruses1999-49152020-03-0112438710.3390/v12040387The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus CapsidNicole Upfold0Caroline Ross1Özlem Tastan Bishop2Caroline Knox3Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South AfricaResearch Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South AfricaResearch Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South AfricaDepartment of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South AfricaThe assembly of picornavirus capsids proceeds through the stepwise oligomerization of capsid protein subunits and depends on interactions between critical residues known as hotspots. Few studies have described the identification of hotspot residues at the protein subunit interfaces of the picornavirus capsid, some of which could represent novel drug targets. Using a combination of accessible web servers for hotspot prediction, we performed a comprehensive bioinformatic analysis of the hotspot residues at the intraprotomer, interprotomer and interpentamer interfaces of the Theiler’s murine encephalomyelitis virus (TMEV) capsid. Significantly, many of the predicted hotspot residues were found to be conserved in representative viruses from different genera, suggesting that the molecular determinants of capsid assembly are conserved across the family. The analysis presented here can be applied to any icosahedral structure and provides a platform for in vitro mutagenesis studies to further investigate the significance of these hotspots in critical stages of the virus life cycle with a view to identify potential targets for antiviral drug design.https://www.mdpi.com/1999-4915/12/4/387assemblyaxis of symmetrycapsidcardiovirushotspotpentamer |
| spellingShingle | Nicole Upfold Caroline Ross Özlem Tastan Bishop Caroline Knox The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid Viruses assembly axis of symmetry capsid cardiovirus hotspot pentamer |
| title | The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid |
| title_full | The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid |
| title_fullStr | The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid |
| title_full_unstemmed | The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid |
| title_short | The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid |
| title_sort | in silico prediction of hotspot residues that contribute to the structural stability of subunit interfaces of a picornavirus capsid |
| topic | assembly axis of symmetry capsid cardiovirus hotspot pentamer |
| url | https://www.mdpi.com/1999-4915/12/4/387 |
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