Structure-based nuclear import mechanism of histones H3 and H4 mediated by Kap123
- University of Michigan Medical School, United States
- Korea Advanced Institute of Science and Technology, Korea (South), Republic of
Abstract
Kap123, a major karyopherin protein of budding yeast, recognizes the nuclear localization signals (NLSs) of cytoplasmic histones H3 and H4 and translocates them into the nucleus during DNA replication. Mechanistic questions include H3- and H4-NLS redundancy toward Kap123 and the role of the conserved diacetylation of cytoplasmic H4 (K5ac and K12ac) in Kap123-mediated histone nuclear translocation. Here, we report crystal structures of full-length Kluyveromyces lactis Kap123 alone and in complex with H3- and H4-NLSs. Structures reveal the unique feature of Kap123 that possesses two discrete lysine-binding pockets for NLS recognition. Structural comparison illustrates that H3- and H4-NLSs share at least one of two lysine-binding pockets, suggesting that H3- and H4-NLSs are mutually exclusive. Additionally, acetylation of key lysine residues at NLS, particularly H4-NLS diacetylation, weakens the interaction with Kap123. These data support that cytoplasmic histone H4 diacetylation weakens the Kap123-H4-NLS interaction thereby facilitating histone Kap123-H3-dependent H3:H4/Asf1 complex nuclear translocation.
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Funding
National Institutes of Health (DK111465)
- Uhn-soo Cho
American Diabetes Association (1-16-JDF-017)
- Uhn-soo Cho
National Institutes of Health (AG050903)
- Uhn-soo Cho
March of Dimes Foundation (N019154-00)
- Uhn-soo Cho
National Research Foundation of Korea (2016R1A2B3006293)
- Ji-Joon Song
National Research Foundation of Korea (2013R1A1A2055605)
- Ji-Joon Song
National Research Foundation of Korea (2014K2A3A1000137)
- Ji-Joon Song
National Research Foundation of Korea (2011-0031955)
- Ji-Joon Song
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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© 2017, An 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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Structure-based nuclear import mechanism of histones H3 and H4 mediated by Kap123
eLife 6:e30244.
https://doi.org/10.7554/eLife.30244
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