Choi Saehae, Yamashita Eiki, Yasuhara Noriko, Song Jinsue, Son Se-Young, Won Young Han, Hong Hye Rim, Shin Yoon Sik, Sekimoto Toshihiro, Park Il Yeong, Yoneda Yoshihiro, Lee Soo Jae
College of Pharmacy, Chungbuk National University, Seungbong 410, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Institute for Protein Research, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Acta Crystallogr D Biol Crystallogr. 2014 Apr;70(Pt 4):1050-60. doi: 10.1107/S1399004714000972. Epub 2014 Mar 19.
Snail contributes to the epithelial-mesenchymal transition by suppressing E-cadherin in transcription processes. The Snail C2H2-type zinc-finger (ZF) domain functions both as a nuclear localization signal which binds to importin β directly and as a DNA-binding domain. Here, a 2.5 Å resolution structure of four ZF domains of Snail1 complexed with importin β is presented. The X-ray structure reveals that the four ZFs of Snail1 are required for tight binding to importin β in the nuclear import of Snail1. The shape of the ZFs in the X-ray structure is reminiscent of a round snail, where ZF1 represents the head, ZF2-ZF4 the shell, showing a novel interaction mode, and the five C-terminal residues the tail. Although there are many kinds of C2H2-type ZFs which have the same fold as Snail, nuclear import by direct recognition of importin β is observed in a limited number of C2H2-type ZF proteins such as Snail, Wt1, KLF1 and KLF8, which have the common feature of terminating in ZF domains with a short tail of amino acids.
Snail通过在转录过程中抑制E-钙黏蛋白来促进上皮-间质转化。Snail的C2H2型锌指（ZF）结构域既作为直接与输入蛋白β结合的核定位信号，又作为DNA结合结构域。在此，展示了Snail1的四个ZF结构域与输入蛋白β复合的分辨率为2.5 Å的结构。X射线结构表明，Snail1的四个ZF对于Snail1核输入过程中与输入蛋白β的紧密结合是必需的。X射线结构中ZF的形状让人联想到一只圆圆的蜗牛，其中ZF1代表头部，ZF2-ZF4代表外壳，呈现出一种新颖的相互作用模式，而五个C末端残基代表尾巴。尽管有许多种类的C2H2型ZF与Snail具有相同的折叠结构，但通过直接识别输入蛋白β进行核输入仅在少数C2H2型ZF蛋白中观察到，如Snail、Wt1、KLF1和KLF8，它们的共同特征是以带有短氨基酸尾巴的ZF结构域结尾。
