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 beta directly and as a DNA-binding domain. Here, a 2.5 angstrom resolution structure of four ZF domains of Snail1 complexed with importin beta is presented. The X-ray structure reveals that the four ZFs of Snail1 are required for tight binding to importin beta 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 beta 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.