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

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.
Mesh Terms:
Active Transport, Cell Nucleus, Allosteric Site, Apoptosis Regulatory Proteins, Cell Nucleus, Circular Dichroism, Cytoplasm, Hematopoiesis, Humans, In Situ Hybridization, Fluorescence, Karyopherins, Magnetic Resonance Spectroscopy, Mass Spectrometry, Mutation, Nuclear Proteins, Phenotype, Protein Binding, Protein Conformation, RNA, Recombinant Proteins, Ribosomal Proteins, Ribosomes, Saccharomyces cerevisiae, ran GTP-Binding Protein
Nat Commun
Date: Dec. 10, 2017
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