9QOO

Composite model: Ternary complex of the human 20S proteasome in complex with Importin-9 and two homodimers of Akirin-2

Summary for 9QOO

• Entry DOI: 10.2210/pdb9qoo/pdb
• Related: 9QNO 9QON
• EMDB information: 53265
• Descriptor: Importin-9, Akirin-2, Proteasome subunit alpha type-3, ... (9 entities in total)
• Functional Keywords: 20s proteasome, 20s, proteasome, nuclear iport, akirin, akirin2, importin 9, importin, protein transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 401481.23

Authors

Brunner, H.L.,Grundmann, L.,David, H. (deposition date: 2025-03-26, release date: 2026-01-28, Last modification date: 2026-02-18)

Primary citation

Brunner, H.L.,Kalis, R.W.,Grundmann, L.,Hodakova, Z.,Koskova, Z.,Grishkovskaya, I.,de Almeida, M.,Hinterndorfer, M.,Knaudt, H.,Hofflin, S.,Andersch, F.,Kotisch, H.,Dickmanns, A.,Cuylen-Haering, S.,Zuber, J.,Haselbach, D.
A multivalent adaptor mechanism drives the nuclear import of proteasomes.
Nat Commun, 2026

PubMed Abstract: Nuclear protein homeostasis, including transcription factor turnover, critically depends on the nuclear proteasomes that must be imported after cell division. This dynamic process requires AKIRIN2, a small unstructured protein whose mechanistic role has remained elusive despite its essential function. Using an integrated approach combining protein-wide saturation mutagenesis screens, cryo-EM, and biochemical reconstitution, we characterize AKIRIN2 as a scaffold protein that coordinates the assembly of an importin cluster around the proteasome. AKIRIN2 binds in multiple copies to the 20S proteasome and simultaneously interacts with importin IPO9 and the KPNA2/KPNB1 heterodimer. In the nucleus, RanGTP triggers importin dissociation, releasing the proteasome, while AKIRIN2 undergoes ubiquitin-independent degradation. Our findings reveal how AKIRIN2's multivalency facilitates the recruitment of multiple importins to the proteasome, a critical adaptation for transporting this large macromolecular complex into the nucleus and maintaining the nuclear proteome.

PubMed: 41639071
DOI: 10.1038/s41467-026-69162-0

Experimental method

ELECTRON MICROSCOPY (3.3 Å)