| Structural highlights
Function
[FTZF1_DROME] Acts as a cofactor to fushi tarazu (ftz). Facilitates the binding of ftz to DNA. Binds the sequence element 5'-YCYYGGYCR-3' in the zebra element of ftz. Probably also functions as a receptor for a yet unknown ligand.[1] [2] [FTZ_DROME] May play a role in determining neuronal identity, may be directly involved in specifying identity of individual neurons. Required during embryogenesis for the process of body segmentation. Homeotic protein, required in alternating segment primordia, it specifies the correct number of segments.[3] [4] [5]
Publication Abstract from PubMed
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.
Crystal structure of fushi tarazu factor 1 ligand binding domain/fushi tarazu Peptide complex identifies new class of nuclear receptors.,Yoo J, Ko S, Kim H, Sampson H, Yun JH, Choe KM, Chang I, Arrowsmith CH, Krause HM, Cho HS, Lee W J Biol Chem. 2011 Sep 9;286(36):31225-31. Epub 2011 Jul 20. PMID:21775434[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Guichet A, Copeland JW, Erdelyi M, Hlousek D, Zavorszky P, Ho J, Brown S, Percival-Smith A, Krause HM, Ephrussi A. The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors. Nature. 1997 Feb 6;385(6616):548-52. PMID:9020363 doi:http://dx.doi.org/10.1038/385548a0
- ↑ Yu Y, Li W, Su K, Yussa M, Han W, Perrimon N, Pick L. The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein Ftz. Nature. 1997 Feb 6;385(6616):552-5. PMID:9020364 doi:http://dx.doi.org/10.1038/385552a0
- ↑ Laughon A, Scott MP. Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins. Nature. 1984 Jul 5-11;310(5972):25-31. PMID:6330566
- ↑ Doe CQ, Hiromi Y, Gehring WJ, Goodman CS. Expression and function of the segmentation gene fushi tarazu during Drosophila neurogenesis. Science. 1988 Jan 8;239(4836):170-5. PMID:2892267
- ↑ Krause HM, Klemenz R, Gehring WJ. Expression, modification, and localization of the fushi tarazu protein in Drosophila embryos. Genes Dev. 1988 Aug;2(8):1021-36. PMID:3049237
- ↑ Yoo J, Ko S, Kim H, Sampson H, Yun JH, Choe KM, Chang I, Arrowsmith CH, Krause HM, Cho HS, Lee W. Crystal structure of fushi tarazu factor 1 ligand binding domain/fushi tarazu Peptide complex identifies new class of nuclear receptors. J Biol Chem. 2011 Sep 9;286(36):31225-31. Epub 2011 Jul 20. PMID:21775434 doi:10.1074/jbc.M111.252916
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