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Solution structure of the zinc finger HIT domain in protein FON
Author(s) -
He Fahu,
Umehara Takashi,
Tsuda Kengo,
Inoue Makoto,
Kigawa Takanori,
Matsuda Takayoshi,
Yabuki Takashi,
Aoki Masaaki,
Seki Eiko,
Terada Takaho,
Shirouzu Mikako,
Tanaka Akiko,
Sugano Sumio,
Muto Yutaka,
Yokoyama Shigeyuki
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.062635107
Subject(s) - zinc finger , lim domain , zinc , ring finger domain , antiparallel (mathematics) , phd finger , crystallography , chemistry , protein structure , ring finger , structural motif , physics , gene , transcription factor , biochemistry , organic chemistry , quantum mechanics , magnetic field
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 Å for the structured residues 12–48. The fold consists of two consecutive antiparallel β‐sheets and two short C‐terminal helices packed against the second β‐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.