Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States.
Department of Biological Sciences, University of Texas at Dallas, Richardson, United States.
Elife. 2019 Mar 11;8:e43630. doi: 10.7554/eLife.43630.
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.
我们报告了核输入受体 Importin-9 与其货物组蛋白 H2A-H2B 结合的晶体结构。Importin-9 围绕 H2A-H2B 的核心球状区域包裹，形成广泛的界面。这种界面的性质以及对 H2A-H2B 缺失突变体的定量分析表明，NLS 样序列在 H2A-H2B 尾部在输入中起次要作用。Importin-9•H2A-H2B 让人联想到组蛋白与其组蛋白伴侣之间的相互作用，因为它阻止了 H2A-H2B 与 DNA 的相互作用，如核小体中所见的 H3-H4。与许多防止不适当的非核小体相互作用的组蛋白伴侣一样，Importin-9 也将 H2A-H2B 与 DNA 隔离。Importin-9 似乎在将 H2A-H2B 护送进核的同时，充当 H2A-H2B 的储存伴侣。令人惊讶的是，RanGTP 不会使 Importin-9•H2A-H2B 解离，而是组装成 RanGTP•Importin-9•H2A-H2B 复合物。然而，复合物中存在的 Ran 调节了 Imp9-H2A-H2B 的相互作用，以促进其通过 DNA 的解离和组装成核小体。
