Conformational variability of nucleo-cytoplasmic transport factors
Conformational variability of nucleo-cytoplasmic transport factors
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DOI：
10.1074/jbc.m309112200
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发表时间：
2004-01-16
影响因子：
4.8
通讯作者：
Svergun, D
中科院分区：
文献类型：
--
作者：
Fukuhara, N;Fernandez, E;Svergun, D
大分子在真核细胞的胞核和胞浆之间的运输主要是由一个单一的运输因子家族介导的，即核粘附素或Importinβ样家族。结构和生化证据表明，这些模块化热重复蛋白的构象灵活性对它们的调控至关重要。在这里，我们使用小角x射线散射来评估一组核进出口因子中构象变化的程度。研究表明，输入素β、转运素和出口素XPO-t在非结合状态下具有类似S的超螺旋构象。在总体结构上没有明显的差异，这些结构大体上可以区分核出口和核进口调解人。该家族的另外两个成员，Exportins Cse1和Xpo1，具有明显更球形的构象，表明扩展的S样结构并不是所有核粘连蛋白的标志。RanGTP/Cargo与Importinβ、Transportin和XPO-t的结合触发了不同的构象反应，这表明即使是密切相关的核粘连蛋白也使用不同的构象调节机制，不同受体的Cargo和核孔相互作用表面可能是唯一的。
The transport of macromolecules between the nucleus and cytoplasm of eukaryotic cells is largely mediated by a single family of transport factors, the karyopherin or importin beta-like family. Structural and biochemical evidence suggests conformational flexibility of these modular HEAT-repeat proteins is crucial for their regulation. Here we use small angle x-ray scattering to assess the extent of conformational variation within a set of nuclear import and export factors. The study reveals that importin beta, transportin, and the exportin Xpo-t share a similar S-like superhelical conformation in their unbound state. There are no obvious differences in the overall structures that might generally distinguish nuclear export from nuclear import mediators. Two other members of the family, the exportins Cse1 and Xpo1, possess a significantly more globular conformation, indicating that the extended S-like architecture is not a hallmark of all karyopherins. Binding of RanGTP/cargo to importin beta, transportin, and Xpo-t triggers distinct conformational responses, suggesting that even closely related karyopherins employ different mechanisms of conformational regulation and that cargo and nuclear pore-interacting surfaces of the different receptors may be unique.