Biological impact of mutually exclusive exon switching.
Alternative splicing can expand the diversity of proteomes. Homologous mutually exclusive exons (MXEs) originate from the same ancestral exon and result in polypeptides with similar structural properties but altered sequence. Why would some genes switch homologous exons and what are their biological...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1008708 |
| _version_ | 1819260794673561600 |
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| author | Su Datt Lam M Madan Babu Jonathan Lees Christine A Orengo |
| author_facet | Su Datt Lam M Madan Babu Jonathan Lees Christine A Orengo |
| author_sort | Su Datt Lam |
| collection | DOAJ |
| description | Alternative splicing can expand the diversity of proteomes. Homologous mutually exclusive exons (MXEs) originate from the same ancestral exon and result in polypeptides with similar structural properties but altered sequence. Why would some genes switch homologous exons and what are their biological impact? Here, we analyse the extent of sequence, structural and functional variability in MXEs and report the first large scale, structure-based analysis of the biological impact of MXE events from different genomes. MXE-specific residues tend to map to single domains, are highly enriched in surface exposed residues and cluster at or near protein functional sites. Thus, MXE events are likely to maintain the protein fold, but alter specificity and selectivity of protein function. This comprehensive resource of MXE events and their annotations is available at: http://gene3d.biochem.ucl.ac.uk/mxemod/. These findings highlight how small, but significant changes at critical positions on a protein surface are exploited in evolution to alter function. |
| first_indexed | 2024-12-23T19:31:34Z |
| format | Article |
| id | doaj.art-77cc1c2c231a4d8f8caa9f0cd1a389b1 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-23T19:31:34Z |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-77cc1c2c231a4d8f8caa9f0cd1a389b12022-12-21T17:33:53ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-03-01173e100870810.1371/journal.pcbi.1008708Biological impact of mutually exclusive exon switching.Su Datt LamM Madan BabuJonathan LeesChristine A OrengoAlternative splicing can expand the diversity of proteomes. Homologous mutually exclusive exons (MXEs) originate from the same ancestral exon and result in polypeptides with similar structural properties but altered sequence. Why would some genes switch homologous exons and what are their biological impact? Here, we analyse the extent of sequence, structural and functional variability in MXEs and report the first large scale, structure-based analysis of the biological impact of MXE events from different genomes. MXE-specific residues tend to map to single domains, are highly enriched in surface exposed residues and cluster at or near protein functional sites. Thus, MXE events are likely to maintain the protein fold, but alter specificity and selectivity of protein function. This comprehensive resource of MXE events and their annotations is available at: http://gene3d.biochem.ucl.ac.uk/mxemod/. These findings highlight how small, but significant changes at critical positions on a protein surface are exploited in evolution to alter function.https://doi.org/10.1371/journal.pcbi.1008708 |
| spellingShingle | Su Datt Lam M Madan Babu Jonathan Lees Christine A Orengo Biological impact of mutually exclusive exon switching. PLoS Computational Biology |
| title | Biological impact of mutually exclusive exon switching. |
| title_full | Biological impact of mutually exclusive exon switching. |
| title_fullStr | Biological impact of mutually exclusive exon switching. |
| title_full_unstemmed | Biological impact of mutually exclusive exon switching. |
| title_short | Biological impact of mutually exclusive exon switching. |
| title_sort | biological impact of mutually exclusive exon switching |
| url | https://doi.org/10.1371/journal.pcbi.1008708 |
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