Solution structure of the zinc finger HIT domain in protein FON.

Abstract

The zinc finger HIT domain is a sequence motif found in many proteins, including thyroid hormone receptor interacting protein 3 (TRIP-3), which is possibly involved in maturity-onset diabetes of the young (MODY). Novel zinc finger motifs are suggested to play important roles in gene regulation and chromatin remodeling. Here, we determined the high-resolution solution structure of the zinc finger HIT domain in ZNHIT2 (protein FON) from Homo sapiens, by an NMR method based on 567 upper distance limits derived from NOE intensities measured in three-dimensional NOESY spectra. The structure yielded a backbone RMSD to the mean coordinates of 0.19 A for the structured residues 12-48. The fold consists of two consecutive antiparallel beta-sheets and two short C-terminal helices packed against the second beta-sheet, and binds two zinc ions. Both zinc ions are coordinated tetrahedrally via a CCCC-CCHC motif to the ligand residues of the zf-HIT domain in an interleaved manner. The tertiary structure of the zinc finger HIT domain closely resembles the folds of the B-box, RING finger, and PHD domains with a cross-brace zinc coordination mode, but is distinct from them. The unique three-dimensional structure of the zinc finger HIT domain revealed a novel zinc-binding fold, as a new member of the treble clef domain family. On the basis of the structural data, we discuss the possible functional roles of the zinc finger HIT domain.

• Authors: Fahu He, Takashi Umehara, Kengo Tsuda, Makoto Inoue, Takanori Kigawa, Takayoshi Matsuda, Takashi Yabuki, Masaaki Aoki, Eiko Seki, Takaho Terada, Mikako Shirouzu, Akiko Tanaka, Sumio Sugano, Yutaka Muto, Shigeyuki Yokoyama
• Journal: Protein science : a publication of the Protein Society (Protein Sci) Vol. 16 Issue 8 Pg. 1577-87 (Aug 2007) ISSN: 0961-8368 [Print] United States
• PMID: 17656577 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphoproteins
• Solutions
• ZNHIT2 protein, human
• Zinc

Topics

• Amino Acid Sequence
• Consensus Sequence
• Humans
• Models, Molecular
• Molecular Sequence Data
• Nuclear Magnetic Resonance, Biomolecular
• Phosphoproteins (chemistry, metabolism)
• Protein Structure, Secondary
• Protein Structure, Tertiary
• Sequence Alignment
• Solutions (chemistry)
• Surface Properties
• Zinc (chemistry, metabolism)
• Zinc Fingers