7LET

Structure of importin a2 bound to the p50- and p65-NLSs

Summary for 7LET

• Entry DOI: 10.2210/pdb7let/pdb
• Related: 7LEQ
• Descriptor: Importin subunit alpha-1, Nuclear factor NF-kappa-B p105 subunit, Transcription factor p65, ... (4 entities in total)
• Functional Keywords: nuclear import, importin alpha, nls, nf-kb, p50, p65, protein transport
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 51066.58

Authors

Florio, T.J.,Lokareddy, R.K.,Cingolani, G. (deposition date: 2021-01-15, release date: 2022-01-19, Last modification date: 2023-10-18)

Primary citation

Florio, T.J.,Lokareddy, R.K.,Yeggoni, D.P.,Sankhala, R.S.,Ott, C.A.,Gillilan, R.E.,Cingolani, G.
Differential recognition of canonical NF-kappa B dimers by Importin alpha 3.
Nat Commun, 13:1207-1207, 2022

PubMed Abstract: Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. In unstimulated cells, p50/p65 is retained by the inhibitor IκBα in the cytoplasm that masks the p65-nuclear localization sequence (NLS). Upon activation, p50/p65 is translocated into the nucleus by the adapter importin α3 and the receptor importin β. Here, we describe a bipartite NLS in p50/p65, analogous to nucleoplasmin NLS but exposed in trans. Importin α3 accommodates the p50- and p65-NLSs at the major and minor NLS-binding pockets, respectively. The p50-NLS is the predominant binding determinant, while the p65-NLS induces a conformational change in the Armadillo 7 of importin α3 that stabilizes a helical conformation of the p65-NLS. Neither conformational change was observed for importin α1, which makes fewer bonds with the p50/p65 NLSs, explaining the preference for α3. We propose that importin α3 discriminates between the transcriptionally active p50/p65 heterodimer and p50/p50 and p65/65 homodimers, ensuring fidelity in NF-κB signaling.

PubMed: 35260573
DOI: 10.1038/s41467-022-28846-z

Experimental method

X-RAY DIFFRACTION (2.4 Å)