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

Natália Elisa Bernardes, Ho Yee Joyce Fung, Yang Li, Zhe Chen, Yuh Min Chook

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Article numbere2207177119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
StatePublished - Sep 20 2022


  • histones
  • importin
  • karyopherins
  • nuclear import
  • nucleosome

ASJC Scopus subject areas

  • General


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