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

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Bernardes NE, Fung HYJ, Li Y, Chen Z, Chook YM
OpenAccess logo Proc Natl Acad Sci U S A 119 e2207177119 (2022)
Cited: 7 times
EuropePMC logo PMID: 36103578

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.

Reviews citing this publication (2)

  1. Nuclear transport proteins: structure, function, and disease relevance. Yang Y, Guo L, Chen L, Gong B, Jia D, Sun Q. Signal Transduct Target Ther 8 425 (2023)
  2. Nuclear-import receptors as gatekeepers of pathological phase transitions in ALS/FTD. Khalil B, Linsenmeier M, Smith CL, Shorter J, Rossoll W. Mol Neurodegener 19 8 (2024)

Articles citing this publication (5)



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