Tsr4 and Nap1, two novel members of the ribosomal protein chaperOME

Nucleic Acids Res. 2019 Jul 26;47(13):6984-7002. doi: 10.1093/nar/gkz317.


Dedicated chaperones protect newly synthesized ribosomal proteins (r-proteins) from aggregation and accompany them on their way to assembly into nascent ribosomes. Currently, only nine of the ∼80 eukaryotic r-proteins are known to be guarded by such chaperones. In search of new dedicated r-protein chaperones, we performed a tandem-affinity purification based screen and looked for factors co-enriched with individual small subunit r-proteins. We report the identification of Nap1 and Tsr4 as direct binding partners of Rps6 and Rps2, respectively. Both factors promote the solubility of their r-protein clients in vitro. While Tsr4 is specific for Rps2, Nap1 has several interaction partners including Rps6 and two other r-proteins. Tsr4 binds co-translationally to the essential, eukaryote-specific N-terminal extension of Rps2, whereas Nap1 interacts with a large, mostly eukaryote-specific binding surface of Rps6. Mutation of the essential Tsr4 and deletion of the non-essential Nap1 both enhance the 40S synthesis defects of the corresponding r-protein mutants. Our findings highlight that the acquisition of eukaryote-specific domains in r-proteins was accompanied by the co-evolution of proteins specialized to protect these domains and emphasize the critical role of r-protein chaperones for the synthesis of eukaryotic ribosomes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Models, Molecular
  • Molecular Chaperones / isolation & purification
  • Molecular Chaperones / pharmacology
  • Molecular Chaperones / physiology*
  • Nucleosome Assembly Protein 1 / physiology*
  • Organelle Biogenesis
  • Protein Binding
  • Protein Biosynthesis
  • Protein Conformation
  • Protein Domains
  • Protein Interaction Mapping
  • Recombinant Fusion Proteins / metabolism
  • Ribosomal Proteins / metabolism*
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / isolation & purification
  • Saccharomyces cerevisiae Proteins / pharmacology
  • Saccharomyces cerevisiae Proteins / physiology*
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Molecular Chaperones
  • NAP1 protein, S cerevisiae
  • Nucleosome Assembly Protein 1
  • Recombinant Fusion Proteins
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • TSR4 protein, S cerevisiae