Protein codes promote selective subcellular compartmentalization
Cells have evolved mechanisms to distribute ~10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must assemble. Here, we demonstrate that proteins with shared functions share amino acid sequence codes that guide them to compartment destinat...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Association for the Advancement of Science
2025
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| Online Access: | https://hdl.handle.net/1721.1/158180 |
| _version_ | 1824458435773595648 |
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| author | Kilgore, Henry R. Chinn, Itamar Mikhael, Peter G. Mitnikov, Ilan Van Dongen, Catherine Zylberberg, Guy Afeyan, Lena Banani, Salman F. Wilson-Hawken, Susana Ihn Lee, Tong Barzilay, Regina Young, Richard A. |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Kilgore, Henry R. Chinn, Itamar Mikhael, Peter G. Mitnikov, Ilan Van Dongen, Catherine Zylberberg, Guy Afeyan, Lena Banani, Salman F. Wilson-Hawken, Susana Ihn Lee, Tong Barzilay, Regina Young, Richard A. |
| author_sort | Kilgore, Henry R. |
| collection | MIT |
| description | Cells have evolved mechanisms to distribute ~10 billion protein molecules to
subcellular compartments where diverse proteins involved in shared functions must
assemble. Here, we demonstrate that proteins with shared functions share amino
acid sequence codes that guide them to compartment destinations. A protein
language model, ProtGPS, was developed that predicts with high performance the
compartment localization of human proteins excluded from the training set.
ProtGPS successfully guided generation of novel protein sequences that selectively
assemble in the nucleolus. ProtGPS identified pathological mutations that change
this code and lead to altered subcellular localization of proteins. Our results
indicate that protein sequences contain not only a folding code, but also a
previously unrecognized code governing their distribution to diverse subcellular
compartments. |
| first_indexed | 2025-02-19T04:25:51Z |
| format | Article |
| id | mit-1721.1/158180 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2025-02-19T04:25:51Z |
| publishDate | 2025 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | mit-1721.1/1581802025-02-06T17:38:13Z Protein codes promote selective subcellular compartmentalization Kilgore, Henry R. Chinn, Itamar Mikhael, Peter G. Mitnikov, Ilan Van Dongen, Catherine Zylberberg, Guy Afeyan, Lena Banani, Salman F. Wilson-Hawken, Susana Ihn Lee, Tong Barzilay, Regina Young, Richard A. Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Abdul Latif Jameel Clinic for Machine Learning in Health Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Computational and Systems Biology Program Cells have evolved mechanisms to distribute ~10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must assemble. Here, we demonstrate that proteins with shared functions share amino acid sequence codes that guide them to compartment destinations. A protein language model, ProtGPS, was developed that predicts with high performance the compartment localization of human proteins excluded from the training set. ProtGPS successfully guided generation of novel protein sequences that selectively assemble in the nucleolus. ProtGPS identified pathological mutations that change this code and lead to altered subcellular localization of proteins. Our results indicate that protein sequences contain not only a folding code, but also a previously unrecognized code governing their distribution to diverse subcellular compartments. 2025-02-06T17:38:11Z 2025-02-06T17:38:11Z 2025-02-06 Article http://purl.org/eprint/type/JournalArticle 1095-9203 https://hdl.handle.net/1721.1/158180 Kilgore, Henry R., Chinn, Itamar, Mikhael, Peter G., Mitnikov, Ilan, Van Dongen, Catherine et al. 2025. "Protein codes promote selective subcellular compartmentalization." Science. en_US https://doi.org/10.1126/science.adq2634 Science Creative Commons Attribution-Noncommercial-ShareAlike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science MIT News |
| spellingShingle | Kilgore, Henry R. Chinn, Itamar Mikhael, Peter G. Mitnikov, Ilan Van Dongen, Catherine Zylberberg, Guy Afeyan, Lena Banani, Salman F. Wilson-Hawken, Susana Ihn Lee, Tong Barzilay, Regina Young, Richard A. Protein codes promote selective subcellular compartmentalization |
| title | Protein codes promote selective subcellular compartmentalization |
| title_full | Protein codes promote selective subcellular compartmentalization |
| title_fullStr | Protein codes promote selective subcellular compartmentalization |
| title_full_unstemmed | Protein codes promote selective subcellular compartmentalization |
| title_short | Protein codes promote selective subcellular compartmentalization |
| title_sort | protein codes promote selective subcellular compartmentalization |
| url | https://hdl.handle.net/1721.1/158180 |
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