2. Academic Validation
  3. Integrative Structural Investigation on the Architecture of Human Importin4_Histone H3/H4_Asf1a Complex and Its Histone H3 Tail Binding

Integrative Structural Investigation on the Architecture of Human Importin4_Histone H3/H4_Asf1a Complex and Its Histone H3 Tail Binding

  • J Mol Biol. 2018 Mar 16;430(6):822-841. doi: 10.1016/j.jmb.2018.01.015.
Jungmin Yoon 1,  Seung Joong Kim 2,  Sojin An 3,  Saehyun Cho 1,  Alexander Leitner 4,  Taeyang Jung 5,  Ruedi Aebersold 6,  Hans Hebert 7,  Uhn-Soo Cho 3,  Ji-Joon Song 8
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
  • 2 Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 3 Department of Biological Chemistry, University of Michigan Medical School, 1150 W. Medical Center Dr., SPC 5606, Ann Arbor, MI 48109, USA.
  • 4 Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
  • 5 Department of Biological Sciences, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea; Department of Biosciences and Nutrition, Karolinska Institutet, and School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Novum, SE-141 57, Sweden.
  • 6 Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland; Faculty of Science, University of Zurich, Zurich, Switzerland.
  • 7 Department of Biosciences and Nutrition, Karolinska Institutet, and School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Novum, SE-141 57, Sweden.
  • 8 Department of Biological Sciences, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea. Electronic address: [email protected].
PMID: 29408485 DOI: 10.1016/j.jmb.2018.01.015
Abstract

Importin4 transports histone H3/H4 in complex with Asf1a to the nucleus for chromatin assembly. Importin4 recognizes the nuclear localization sequence located at the N-terminal tail of histones. Here, we analyzed the structures and interactions of human Importin4, histones and Asf1a by cross-linking mass spectrometry, X-ray crystallography, negative-stain electron microscopy, small-angle X-ray scattering and integrative modeling. The cross-linking mass spectrometry data showed that the C-terminal region of Importin4 was extensively cross-linked with the histone H3 tail. We determined the crystal structure of the C-terminal region of Importin4 bound to the histone H3 peptide, thus revealing that the acidic patch in Importin4 accommodates the histone H3 tail, and that histone H3 Lys14 contributes to the interaction with Importin4. In addition, we show that Asf1a modulates the binding of histone H3/H4 to Importin4. Furthermore, the molecular architecture of the Importin4_histone H3/H4_Asf1a complex was produced through an integrative modeling approach. Overall, this work provides structural insights into how Importin4 recognizes histones and their chaperone complex.

Keywords

assembly; chromatin; integrative structure modeling; nuclear localization sequence; nucleosome.

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