Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone

Abhilash Padavannil, Prithwijit Sarkar, Seung Joong Kim, Tolga Cagatay, Jenny Jiou, Chad A Brautigam, Diana R Tomchick, Andrej Sali, Sheena D'Arcy, Yuh Min Chook

Research output: Contribution to journalArticle

Abstract

We report the crystal structure of nuclear import receptor Importin-9 bound to its cargo, the histones H2A-H2B. Importin-9 wraps around the core, globular region of H2A-H2B to form an extensive interface. The nature of this interface coupled with quantitative analysis of deletion mutants of H2A-H2B suggests that the NLS-like sequences in the H2A-H2B tails play a minor role in import. Importin-9•H2A-H2B is reminiscent of interactions between histones and histone chaperones in that it precludes H2A-H2B interactions with DNA and H3-H4 as seen in the nucleosome. Like many histone chaperones, which prevent inappropriate non-nucleosomal interactions, Importin-9 also sequesters H2A-H2B from DNA. Importin-9 appears to act as a storage chaperone for H2A-H2B while escorting it to the nucleus. Surprisingly, RanGTP does not dissociate Importin-9•H2A-H2B but assembles into a RanGTP•Importin-9•H2A-H2B complex. The presence of Ran in the complex, however, modulates Imp9-H2A-H2B interactions to facilitate its dissociation by DNA and assembly into a nucleosome.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Mar 11 2019

Fingerprint

Histone Chaperones
Karyopherins
Nucleosomes
Histones
DNA
Cell Nucleus Active Transport
Cytoplasmic and Nuclear Receptors
Crystal structure
Chemical analysis

Keywords

  • E. coli
  • H2A-H2B, Ran
  • histone
  • histone chaperone
  • Importin-9
  • karyopherin
  • molecular biophysics
  • nucleosome
  • structural biology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone. / Padavannil, Abhilash; Sarkar, Prithwijit; Kim, Seung Joong; Cagatay, Tolga; Jiou, Jenny; Brautigam, Chad A; Tomchick, Diana R; Sali, Andrej; D'Arcy, Sheena; Chook, Yuh Min.

In: eLife, Vol. 8, 11.03.2019.

Research output: Contribution to journalArticle

Padavannil, Abhilash ; Sarkar, Prithwijit ; Kim, Seung Joong ; Cagatay, Tolga ; Jiou, Jenny ; Brautigam, Chad A ; Tomchick, Diana R ; Sali, Andrej ; D'Arcy, Sheena ; Chook, Yuh Min. / Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone. In: eLife. 2019 ; Vol. 8.
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