@article{17aa0f5c745a4c0b93114fe154c025ae,
title = "Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone",
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.",
author = "Abhilash Padavannil and Prithwijit Sarkar and Kim, {Seung Joong} and Tolga Cagatay and Jenny Jiou and Brautigam, {Chad A.} and Tomchick, {Diana R.} and Andrej Sali and Sheena D{\textquoteright}Arcy and Chook, {Yuh Min}",
note = "Funding Information: We thank Bing Li for plasmids expressing H2A and H2B, Hongtao Yu for the H2BmCherry stable cell lines, Binita Shakya for Ran protein, James Chen for advice on X-ray structure determination, and the Structural Biology Laboratory and Macromolecular Biophysics Resource at UTSW for their assistance with crystallographic and biophysical data collection. Crystallographic results are derived from work performed at Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of Energy (DOE), Office of Biological and Environmental Research (BER) under contract DE-AC02-06CH11357. We thank T Matsui and TM Weiss at SSRL, SLAC National Accelerator Laboratory, for assistance with collecting SAXS data. SAXS experiments were performed at the SSRL, SLAC National Accelerator Laboratory operated for DOE by Stanford University. The SSRL SMBP is supported by the DOE BER, by the National Institutes of Health (NIH), NCRR, Biomedical Technology Program (P41RR001209), and by NIGMS, NIH (P41GM103393). This work was funded by NIGMS of NIH under Awards R01GM069909 (YMC), U01GM98256-01 (YMC and AS), R01GM083960 (AS), P41GM109824 (AS), R01GM112108 (AS), the Welch Foundation Grants I-1532 (YMC), the Leukemia and Lymphoma Society Scholar Award (YMC), start-up funds from the University of Texas at Dallas (SD) and the University of Texas Southwestern Endowed Scholars Program (YMC). Publisher Copyright: {\textcopyright} Padavannil et al.",
year = "2019",
month = mar,
doi = "10.7554/eLife.43630",
language = "English (US)",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}