Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone

eLife

Sheena D'Arcy¹  Andrej Sali²  Prithwijit Sarkar³  Diana R Tomchick⁴  Chad A Brautigam⁴  Yuh Min Chook⁵  Abhilash Padavannil⁶  Tolga Cagatay⁶  Jenny Jiou⁶  Seung Joong Kim⁷ 

[1] Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, United states;Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, United States;Department of Biological Sciences, University of Texas at Dallas, Richardson, United States;Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States;Department of Chemistry and Biochemistry, University of Texas at Dallas, Richardson, United States;Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States;Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea;

关键词: Importin-9;    karyopherin;    histone;    H2A-H2B, Ran;    nucleosome;    histone chaperone;   

DOI  :  10.7554/eLife.43630

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown