title: Solution structures of the DNA-binding domains of immune-related zinc-finger protein ZFAT.
abstract: ZFAT is a transcriptional regulator, containing eighteen C2H2-type zinc-fingers and one AT-hook, involved in autoimmune thyroid disease, apoptosis, and immune-related cell survival. We determined the solution structures of the thirteen individual ZFAT zinc-fingers (ZF) and the tandemly arrayed zinc-fingers in the regions from ZF2 to ZF5, by NMR spectroscopy. ZFAT has eight uncommon bulged-out helix-containing zinc-fingers, and six of their structures (ZF4, ZF5, ZF6, ZF10, ZF11, and ZF13) were determined. The distribution patterns of the putative DNA-binding surface residues are different among the ZFAT zinc-fingers, suggesting the distinct DNA sequence preferences of the N-terminal and C-terminal zinc-fingers. Since ZFAT has three to five consecutive tandem zinc-fingers, which may cooperatively function as a unit, we also determined two tandemly arrayed zinc-finger structures, between ZF2 to ZF4 and ZF3 to ZF5. Our NMR spectroscopic analysis detected the interaction between ZF4 and ZF5, which are connected by an uncommon linker sequence, KKIK. The ZF4-ZF5 linker restrained the relative structural space between the two zinc-fingers in solution, unlike the other linker regions with determined structures, suggesting the involvement of the ZF4-ZF5 interfinger linker in the regulation of ZFAT function.
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.|Department of Mathematical and Life Sciences, Research Center for the Mathematics on Chromatin Live Dynamics, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, 739-8530 Japan.
authors: Naoya
authors: N
authors: Tochio
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.|RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.|PRESTO, Japan Science and Technology Agency (JST), 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.
authors: Takashi
authors: T
authors: Umehara
authors: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, 157-8535 Japan.
authors: Kazuhiko
authors: K
authors: Nakabayashi
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.
authors: Misao
authors: M
authors: Yoneyama
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.|RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.
authors: Kengo
authors: K
authors: Tsuda
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.|RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.
authors: Mikako
authors: M
authors: Shirouzu
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.|Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573 Japan.
authors: Seizo
authors: S
authors: Koshiba
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.|RIKEN Quantitative Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.
authors: Satoru
authors: S
authors: Watanabe
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.|Department of Computational Intelligence and Systems Science, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori, Yokohama, 226-8502 Japan.|RIKEN Quantitative Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.
authors: Takanori
authors: T
authors: Kigawa
authors: Institute for Advanced Studies, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8582 Japan.
authors: Takehiko
authors: T
authors: Sasazuki
authors: Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180 Japan.|Center for Advanced Molecular Medicine, Fukuoka University, Fukuoka, 814-0180 Japan.
authors: Senji
authors: S
authors: Shirasawa
authors: RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.|RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045 Japan.
authors: Shigeyuki
authors: S
authors: Yokoyama
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013967:Thyroiditis, Autoimmune / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C529572:ZFAT protein, human