10SM

Importin-9 bound to ETS homologous factor (EHF)

Summary for 10SM

• Entry DOI: 10.2210/pdb10sm/pdb
• EMDB information: 75437
• Descriptor: ETS homologous factor, Importin-9 (2 entities in total)
• Functional Keywords: nuclear import, importin, dna-binding protein, winged-helix domain, nuclear protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 150999.54

Authors

Bernardes, N.E.,Lankford, K.,McConville, M.,Chook, Y.M.,Liszczak, G. (deposition date: 2026-02-05, release date: 2026-05-27)

Primary citation

McConville, M.,Lankford, K.,Bernardes, N.E.,Walterscheid, A.,Valadez, C.,Niesman, A.,Chook, Y.M.,Liszczak, G.
Importin-9 recognizes the winged-helix fold of ETS transcription factors to mediate nuclear import.
Proc.Natl.Acad.Sci.USA, 123:e2536763123-e2536763123, 2026

PubMed Abstract: Protein trafficking between the cytoplasm and the nucleus is a fundamental process in eukaryotic cell biology. While linear nuclear localization signals (NLSs) are well characterized, many nuclear proteins lack a predictable NLS. Here, we identify the ETS domain, a DNA-binding winged-helix fold, from ETS family transcription factors as a structure-encoded NLS. We show that ETS domains mediate nuclear import through direct nanomolar affinity recognition by IPO9. Cryo-electron microscopy analysis of the EHF:IPO9 complex reveals that the IPO9 wraps around the ETS domain and engages structural features throughout the winged-helix fold. Biochemical studies demonstrate that the ETS domain DNA-binding helix is critical for importin recognition and for NLS activity in mammalian cells. Comparison of IPO9 bound to EHF and the histone H2A:H2B dimer reveals distinct interaction hotspots, illustrating how IPO9 employs unique combinatorial binding surfaces to accommodate structurally diverse cargos. These findings define a unique class of globular NLSs and highlight the adaptability of importins in recognizing distinct protein folds.

PubMed: 42066049
DOI: 10.1073/pnas.2536763123

Experimental method

ELECTRON MICROSCOPY (3.5 Å)