Importin-9 Wraps Around the H2A-H2B Core to Act as Nuclear Importer and Histone Chaperone


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. © 2019 Padavannil et al.



Escherichia coli, Histones, Histone Chaperones, Importin-9, Karyopherins, Molecular biology, Nucleosomes, Biology, Structural

National Institute of General Medical Sciences (U01GM98256-01, R01GM083960, P41GM109824, R01GM112108, R01GM069909); Welch Foundation (I-1532).


CC BY 4.0 (Attribution), ©2019 The Authors