title: Crystal structure of Fushi tarazu factor 1 ligand binding domain/Fushi tarazu peptide complex identifies new class of nuclear receptors.
abstract: The interaction between the orphan nuclear receptor FTZ-F1 (Fushi tarazu factor 1) and the segmentation gene protein FTZ is critical for specifying alternate parasegments in the Drosophila embryo. Here, we have determined the structure of the FTZ-F1 ligand-binding domain (LBD)·FTZ peptide complex using x-ray crystallography. Strikingly, the ligand-binding pocket of the FTZ-F1 LBD is completely occupied by helix 6 (H6) of the receptor, whereas the cofactor FTZ binds the co-activator cleft site of the FTZ-F1 LBD. Our findings suggest that H6 is essential for transcriptional activity of FTZ-F1; this is further supported by data from mutagenesis and activity assays. These data suggest that FTZ-F1 might belong to a novel class of ligand-independent nuclear receptors. Our findings are intriguing given that the highly homologous human steroidogenic factor-1 and liver receptor homolog-1 LBDs exhibit sizable ligand-binding pockets occupied by putative ligand molecules.
authors.affiliation: Department of Biology, College of Life Science and Biotechnology, Yonsei University, Shinchon-dong, Seodaemun-gu 134, Seoul 120-749, Korea.
authors.forename: Jiho
authors.initials: J
authors.lastname: Yoo
authors.forename: Sunggeon
authors.initials: S
authors.lastname: Ko
authors.forename: Hyeyon
authors.initials: H
authors.lastname: Kim
authors.forename: Heidi
authors.initials: H
authors.lastname: Sampson
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yun
authors.forename: Kwang-Min
authors.initials: KM
authors.lastname: Choe
authors.forename: Iksoo
authors.initials: I
authors.lastname: Chang
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Arrowsmith
authors.forename: Henry M
authors.initials: HM
authors.lastname: Krause
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Cho
authors.forename: Weontae
authors.initials: W
authors.lastname: Lee
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008024:Ligands; D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C499712:nuclear hormone receptor FTZ-F1, Drosophila