7UNK

Structure of Importin-4 bound to the H3-H4-ASF1 histone-histone chaperone complex

Summary for 7UNK

• Entry DOI: 10.2210/pdb7unk/pdb
• EMDB information: 26625
• Descriptor: Importin-4, Histone H3, Histone chaperone, ... (4 entities in total)
• Functional Keywords: importin, nuclear import, chaperone, histones, h3, h4, asf1, nuclear protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 177262.83

Authors

Bernardes, N.E.,Chook, Y.M.,Fung, H.Y.J.,Chen, Z.,Li, Y. (deposition date: 2022-04-11, release date: 2022-09-21, Last modification date: 2025-05-28)

Primary citation

Bernardes, N.E.,Fung, H.Y.J.,Li, Y.,Chen, Z.,Chook, Y.M.
Structure of IMPORTIN-4 bound to the H3-H4-ASF1 histone-histone chaperone complex.
Proc.Natl.Acad.Sci.USA, 119:e2207177119-e2207177119, 2022

PubMed Abstract: IMPORTIN-4, the primary nuclear import receptor of core histones H3 and H4, binds the H3-H4 dimer and histone chaperone ASF1 prior to nuclear import. However, how H3-H3-ASF1 is recognized for transport cannot be explained by available crystal structures of IMPORTIN-4-histone tail peptide complexes. Our 3.5-Å IMPORTIN-4-H3-H4-ASF1 cryoelectron microscopy structure reveals the full nuclear import complex and shows a binding mode different from suggested by previous structures. The N-terminal half of IMPORTIN-4 clamps the globular H3-H4 domain and H3 αN helix, while its C-terminal half binds the H3 N-terminal tail weakly; tail contribution to binding energy is negligible. ASF1 binds H3-H4 without contacting IMPORTIN-4. Together, ASF1 and IMPORTIN-4 shield nucleosomal H3-H4 surfaces to chaperone and import it into the nucleus where RanGTP binds IMPORTIN-4, causing large conformational changes to release H3-H4-ASF1. This work explains how full-length H3-H4 binds IMPORTIN-4 in the cytoplasm and how it is released in the nucleus.

PubMed: 36103578
DOI: 10.1073/pnas.2207177119

Experimental method

ELECTRON MICROSCOPY (3.45 Å)