The structure of the nuclear export receptor Cse1 in its cytosolic state reveals a closed conformation incompatible with cargo binding

被引:59
作者
Cook, A
Fernandez, E
Lindner, D
Ebert, J
Schlenstedt, G
Conti, E
机构
[1] European Mol Biol Lab, D-69117 Heidelberg, Germany
[2] Univ Saarland, D-66421 Homburg, Germany
关键词
D O I
10.1016/j.molcel.2005.03.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cse1 mediates nuclear export of importin a, the nuclear localization signal (NLS) import adaptor. We report the 3.1 A resolution structure of cargo-free 1, representing this HEAT repeat protein in its cytosolic state. Cse1 is compact, consisting of N- and C-terminal arches that interact to form a ring. Comparison with the structure of cargo-bound Cse1 shows a major conformational change leading to opening of the structure upon cargo binding. The largest structural changes occur within a hinge region centered at HEAT repeat 8. This repeat contains a conserved insertion that connects the RanGTP and importin alpha contact sites and that is essential for binding. In the cargo-free state, the RanGTP binding sites are occluded and the importin alpha sites are distorted. Mutations that destabilize the N- to C-terminal interaction uncouple importin a and Ran binding, suggesting that the closed conformation prevents association with importin alpha.
引用
收藏
页码:355 / 367
页数:13
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