Structural basis for the selective nuclear import of the C2H2 zinc-finger protein Snail by importin β

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.