8CMK

Transportin-3 TNPO3 in complex with RSY region of CIRBP

Summary for 8CMK

• Entry DOI: 10.2210/pdb8cmk/pdb
• Descriptor: Transportin-3, Cold-inducible RNA-binding protein, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: transportin, nuclear import, rna-binding, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 220690.39

Authors

Zhou, Q.,Sagmeister, T.,Pavkov-Keller, T.,Madl, T. (deposition date: 2023-02-20, release date: 2024-03-06, Last modification date: 2025-06-11)

Primary citation

Zhou, Q.,Sagmeister, T.,Hutten, S.,Bourgeois, B.,Pavkov-Keller, T.,Dormann, D.,Madl, T.
Structural basis of phosphorylation-independent nuclear import of CIRBP by TNPO3.
Nat Commun, 16:4456-4456, 2025

PubMed Abstract: Transportin 3 (TNPO3) is a nuclear import receptor known for its broad substrate specificity, often recognizing arginine-serine (SR/RS) repeat-rich nuclear localization signals (NLS) in SRSF proteins. While serine phosphorylation or glutamate presence has been associated with these NLSs, recent proteomic studies identified TNPO3 cargoes lacking SR/RS repeats. One such example is the cold-inducible RNA-binding protein (CIRBP), which contains a non-classical RSY-NLS. Using X-ray crystallography, here we investigate the TNPO3-CIRBP interaction and find that tyrosines within the RSY-NLS play a key role in binding, independent of phosphorylation. Surprisingly, serine and tyrosine phosphorylation in CIRBP's NLS inhibits TNPO3 binding, suggesting a regulatory mechanism for nuclear import. Our study reveals a non-conventional nuclear import mechanism mediated by TNPO3, which may extend to other known or yet undiscovered TNPO3 cargoes.

PubMed: 40360518
DOI: 10.1038/s41467-025-59802-2

Experimental method

X-RAY DIFFRACTION (2.945 Å)