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.
College of Pharmacy, Chungbuk National University, Seungbong 410, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Saehae
S
Choi
Institute for Protein Research, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Eiki
E
Yamashita
Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Noriko
N
Yasuhara
College of Pharmacy, Chungbuk National University, Seungbong 410, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Jinsue
J
Song
College of Pharmacy, Chungbuk National University, Seungbong 410, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Se-Young
SY
Son
College of Pharmacy, Chungbuk National University, Seungbong 410, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Young Han
YH
Won
College of Pharmacy, Chungbuk National University, Seungbong 410, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Hye Rim
HR
Hong
College of Pharmacy, Chungbuk National University, Seungbong 410, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Yoon Sik
YS
Shin
Department of Biochemistry, Graduate School of Medicine, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Toshihiro
T
Sekimoto
College of Pharmacy, Chungbuk National University, Seungbong 410, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Il Yeong
IY
Park
Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Yoshihiro
Y
Yoneda
College of Pharmacy, Chungbuk National University, Seungbong 410, Heungduk, Cheongju, Chungbuk 361-763, Republic of Korea.
Soo Jae
SJ
Lee
D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers; D028961:beta Karyopherins / Q000737:chemistry* / Q000378:metabolism
C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D028961:beta Karyopherins
Snail; importin β; nuclear transport; zinc-finger domains