Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2

Nat Commun. 2018 Sep 10;9(1):3669. doi: 10.1038/s41467-018-06160-x.


Disordered extensions at the termini and short internal insertions distinguish eukaryotic ribosomal proteins (r-proteins) from their anucleated archaeal counterparts. Here, we report an NMR structure of such a eukaryotic-specific segment (ESS) in the r-protein eS26 in complex with the escortin Tsr2. The structure reveals how ESS attracts Tsr2 specifically to importin:eS26 complexes entering the nucleus in order to trigger non-canonical RanGTP-independent disassembly. Tsr2 then sequesters the released eS26 and prevents rebinding to the importin, providing an alternative allosteric mechanism to terminate the process of nuclear import. Notably, a Diamond-Blackfan anemia-associated Tsr2 mutant protein is impaired in binding to ESS, unveiling a critical role for this interaction in human hematopoiesis. We propose that eS26-ESS and Tsr2 are components of a nuclear sorting system that co-evolved with the emergence of the nucleocytoplasmic barrier and transport carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Allosteric Site
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Circular Dichroism
  • Cytoplasm / metabolism
  • Hematopoiesis
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyopherins / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mutation
  • Nuclear Proteins / metabolism
  • Phenotype
  • Protein Binding
  • Protein Conformation
  • RNA / chemistry
  • Recombinant Proteins / metabolism
  • Ribosomal Proteins / metabolism*
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae
  • ran GTP-Binding Protein / metabolism


  • Apoptosis Regulatory Proteins
  • Karyopherins
  • Nuclear Proteins
  • Recombinant Proteins
  • Ribosomal Proteins
  • TSR2 protein, human
  • RNA
  • ran GTP-Binding Protein