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.
Abhilash Padavannil  1 ,  Prithwijit Sarkar  2 ,  Seung Joong Kim  3 ,  Tolga Cagatay  1 ,  Jenny Jiou  1 ,  Chad A Brautigam  4 ,  Diana R Tomchick  4 ,  Andrej Sali  5  6 ,  Sheena D'Arcy  7 ,  Yuh Min Chook  1
Affiliations
  • 1. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States.
  • 2. Department of Biological Sciences, University of Texas at Dallas, Richardson, United States.
  • 3. Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
  • 4. Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States.
  • 5. Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, United States.
  • 6. Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, United states.
  • 7. Department of Chemistry and Biochemistry, University of Texas at Dallas, Richardson, United States.
PMID: 30855230 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.