Protein codes promote selective subcellular compartmentalization.
Henry R Kilgore1, Itamar Chinn2,3, Peter G Mikhael2,3
1Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Science (New York, N.Y.)
|February 6, 2025
Summary
Cells use amino acid sequence codes to direct proteins to specific compartments. A new model, ProtGPS, predicts protein localization and guides the creation of proteins that assemble in the nucleolus.
Area of Science:
- Cell biology
- Molecular biology
- Bioinformatics
Background:
- Cells must efficiently distribute billions of proteins to specific subcellular compartments.
- Proteins with shared functions often need to assemble together within these compartments.
Purpose of the Study:
- To investigate if amino acid sequences contain codes for subcellular protein distribution.
- To develop a predictive model for protein localization.
- To explore the potential for engineering protein localization.
Main Methods:
- Development of a protein language model, ProtGPS, trained on human protein data.
- Prediction of subcellular compartment localization for proteins outside the training set.
- Guided generation of novel protein sequences with specific localization properties.
Main Results:
- ProtGPS accurately predicts human protein compartment localization.
- Novel protein sequences were successfully generated to target the nucleolus.
- The model identified mutations altering protein subcellular localization.
Conclusions:
- Protein sequences encode a previously unrecognized code for subcellular distribution.
- This code is distinct from the protein folding code.
- Understanding this code has implications for cell biology and disease research.
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