Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains
Abstract The recent progress in the prediction of protein structures marked a historical milestone. AlphaFold predicted 200 million protein models with an accuracy comparable to experimental methods. Protein structures are widely used to understand evolution and to identify potential drug targets fo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-39273-5 |
| _version_ | 1797769486697234432 |
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| author | Kirill E. Medvedev R. Dustin Schaeffer Kenneth S. Chen Nick V. Grishin |
| author_facet | Kirill E. Medvedev R. Dustin Schaeffer Kenneth S. Chen Nick V. Grishin |
| author_sort | Kirill E. Medvedev |
| collection | DOAJ |
| description | Abstract The recent progress in the prediction of protein structures marked a historical milestone. AlphaFold predicted 200 million protein models with an accuracy comparable to experimental methods. Protein structures are widely used to understand evolution and to identify potential drug targets for the treatment of various diseases, including cancer. Thus, these recently predicted structures might convey previously unavailable information about cancer biology. Evolutionary classification of protein domains is challenging and different approaches exist. Recently our team presented a classification of domains from human protein models released by AlphaFold. Here we evaluated the pan-cancer structurome, domains from over and under expressed proteins in 21 cancer types, using the broadest levels of the ECOD classification: the architecture (A-groups) and possible homology (X-groups) levels. Our analysis reveals that AlphaFold has greatly increased the three-dimensional structural landscape for proteins that are differentially expressed in these 21 cancer types. We show that beta sandwich domains are significantly overrepresented and alpha helical domains are significantly underrepresented in the majority of cancer types. Our data suggest that the prevalence of the beta sandwiches is due to the high levels of immunoglobulins and immunoglobulin-like domains that arise during tumor development-related inflammation. On the other hand, proteins with exclusively alpha domains are important elements of homeostasis, apoptosis and transmembrane transport. Therefore cancer cells tend to reduce representation of these proteins to promote successful oncogeneses. |
| first_indexed | 2024-03-12T21:08:45Z |
| format | Article |
| id | doaj.art-27726e4358d04793a10ff059fe94d8d6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T21:08:45Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-27726e4358d04793a10ff059fe94d8d62023-07-30T11:15:51ZengNature PortfolioScientific Reports2045-23222023-07-0113111510.1038/s41598-023-39273-5Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domainsKirill E. Medvedev0R. Dustin Schaeffer1Kenneth S. Chen2Nick V. Grishin3Department of Biophysics, University of Texas Southwestern Medical CenterDepartment of Biophysics, University of Texas Southwestern Medical CenterDepartment of Pediatrics, University of Texas Southwestern Medical CenterDepartment of Biophysics, University of Texas Southwestern Medical CenterAbstract The recent progress in the prediction of protein structures marked a historical milestone. AlphaFold predicted 200 million protein models with an accuracy comparable to experimental methods. Protein structures are widely used to understand evolution and to identify potential drug targets for the treatment of various diseases, including cancer. Thus, these recently predicted structures might convey previously unavailable information about cancer biology. Evolutionary classification of protein domains is challenging and different approaches exist. Recently our team presented a classification of domains from human protein models released by AlphaFold. Here we evaluated the pan-cancer structurome, domains from over and under expressed proteins in 21 cancer types, using the broadest levels of the ECOD classification: the architecture (A-groups) and possible homology (X-groups) levels. Our analysis reveals that AlphaFold has greatly increased the three-dimensional structural landscape for proteins that are differentially expressed in these 21 cancer types. We show that beta sandwich domains are significantly overrepresented and alpha helical domains are significantly underrepresented in the majority of cancer types. Our data suggest that the prevalence of the beta sandwiches is due to the high levels of immunoglobulins and immunoglobulin-like domains that arise during tumor development-related inflammation. On the other hand, proteins with exclusively alpha domains are important elements of homeostasis, apoptosis and transmembrane transport. Therefore cancer cells tend to reduce representation of these proteins to promote successful oncogeneses.https://doi.org/10.1038/s41598-023-39273-5 |
| spellingShingle | Kirill E. Medvedev R. Dustin Schaeffer Kenneth S. Chen Nick V. Grishin Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains Scientific Reports |
| title | Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains |
| title_full | Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains |
| title_fullStr | Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains |
| title_full_unstemmed | Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains |
| title_short | Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains |
| title_sort | pan cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains |
| url | https://doi.org/10.1038/s41598-023-39273-5 |
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