Structural basis for substrate recognition and dissociation by human transportin 1
Structural basis for substrate recognition and dissociation by human transportin 1
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DOI：
10.1016/j.molcel.2007.08.006
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发表时间：
2007-10-12
期刊：
影响因子：
16
通讯作者：
Sato, Mamoru
中科院分区：
文献类型：
--
作者：
Imasaki, Tsuyoshi;Shimizu, Toshiyuki;Sato, Mamoru
转运蛋白1(Trn1)是一种转运受体，通过识别核定位信号(NLSS)，通过核孔复合体将底物从细胞质转运到细胞核。在这里，我们描述了人Trn1的四种晶体结构，在无底物形式以及在三个NLSS(分别为hnRNP D，JKTBP和TAP)的复合体中。我们的数据表明：(1)Trn1有两个结合NLSS的位点，一个是高亲和力的(A位)，另一个是低亲和力的(B位)，而B位的NLS相互作用控制着Trn1的整体结合亲和力；(2)Trn1识别A位的NLSS，然后在B位发生构象变化与NLSS相互作用；(3)Trn1的一个长而灵活的环与13位点相互作用，从而取代核中的运输底物。这些研究为Trn1在输入途径中识别和解离底物提供了深入的理解。
Transportin 1 (Trn1) is a transport receptor that transports substrates from the cytoplasm to the nucleus through nuclear pore complexes by recognizing nuclear localization signals (NLSs). Here we describe four crystal structures of human Trn1 in a substrate-free form as well as in the complex with three NLSs (hnRNP D, JKTBP, and TAP, respectively). Our data have revealed that (1) Trn1 has two sites for binding NLSs, one with high affinity (site A) and one with low affinity (site B), and NLS interaction at site B controls overall binding affinity for Trn1; (2) Trn1 recognizes the NLSs at site A followed by conformational change at site B to interact with the NLSs; and (3) a long flexible loop, characteristic of Trn1, interacts with site 13, thereby displacing transport substrate in the nucleus. These studies provide deep understanding of substrate recognition and dissociation by Trn1 in import pathways.