Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone
- University of Texas Southwestern Medical Center, United States
- University of Texas at Dallas, United States
- Korea Advanced Institute of Science and Technology (KAIST), Korea (South), Republic of
- University of California, San Francisco, United States
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 suggest 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.
Data availability
Diffraction data have been deposited in PDB under the accession code 6N1Z
Article and author information
Author details
Funding
National Institutes of Health
- Yuh Min Chook
Welch Foundation
- Yuh Min Chook
Leukemia and Lymphoma Society
- Yuh Min Chook
National Institutes of Health
- Abhilash Padavannil
- Tolga Cagatay
- Jenny Jiou
National Institutes of Health
- Chad A Brautigam
- Diana R Tomchick
- Andrej Sali
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany
Publication history
- Received: November 14, 2018
- Accepted: March 9, 2019
- Accepted Manuscript published: March 11, 2019 (version 1)
- Version of Record published: April 8, 2019 (version 2)
Copyright
© 2019, Padavannil et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone
eLife 8:e43630.
https://doi.org/10.7554/eLife.43630
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