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. In this study, we demonstrate that proteins with shared functions share amino acid sequence codes that guide them to compartment destinations. We developed a protein language model, ProtGPS, 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…

• NS
  National Science Foundation

  Award: PHY2044895
• DR
  Damon Runyon Cancer Research Foundation

  Award: 2458-22
• BI
  Broad Institute
• NI
  National Institutes of Health