Protein codes promote selective subcellular compartmentalization
Name
Protein_codes_250129.pdf
Size
17.83 MB
Format
Adobe PDF
Checksum (MD5)
1471b2895eae8c767dbf23d91c4d49d4
Author(s)
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
Date Issued
February 6, 2025
Journal
Science
Publisher
American Association for the Advancement of Science
Citation
Kilgore, Henry R., Chinn, Itamar, Mikhael, Peter G., Mitnikov, Ilan, Van Dongen, Catherine et al. 2025. "Protein codes promote selective subcellular compartmentalization." Science.
Version
Author's final manuscript
Abstract
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.
MIT Department
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
Terms of Use
Creative Commons Attribution-Noncommercial-ShareAlike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/science.adq2634
