Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chperone
Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chperone
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DOI：
10.7554/elife.43630
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发表时间：
2019-03-11
期刊：
影响因子：
7.7
通讯作者：
Chook, Yuh Min
中科院分区：
文献类型：
--
作者：
Padavannil, Abhilash;Sarkar, Prithwijit;Chook, Yuh Min
我们报道了核进口受体Importin-9与其货物组蛋白H2A-H2B结合的晶体结构。Importin-9包裹在H2A-H2B的核心球状区域，形成广泛的界面。这种界面的性质加上H2A-H2B缺失突变体的定量分析表明，H2A-H2B尾部的nls样序列在导入中起次要作用。Importin-9中心点H2A-H2B让人联想到组蛋白和组蛋白伴侣之间的相互作用，因为它在核小体中阻止了H2A-H2B与DNA和H3-H4的相互作用。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也从DNA中分离H2A-H2B。Importin-9似乎充当H2A-H2B的储存伴侣，并将其护送到细胞核。令人惊讶的是，RanGTP不会解离Importin-9中心点H2A-H2B，而是组装成RanGTP中心点Importin-9中心点H2A-H2B复合体。然而，Ran在复合物中的存在调节Imp9-H2A-H2B相互作用，促进其被DNA解离并组装成核小体。
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 center dot 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 center dot H2A-H2B but assembles into a RanGTP center dot Importin-9 center dot 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.