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

Elife. 2019 Mar 11;8:e43630. doi: 10.7554/eLife.43630.

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Crystallography, X-Ray
  • DNA Mutational Analysis
  • Histones / chemistry*
  • Histones / metabolism*
  • Humans
  • Karyopherins / chemistry*
  • Karyopherins / genetics
  • Karyopherins / metabolism*
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Protein Binding
  • Protein Conformation
  • Xenopus

Substances

  • Histones
  • Karyopherins
  • Molecular Chaperones
  • Mutant Proteins
  • importin 9, human