Crystal structure of Fushi tarazu factor 1 ligand binding domain/Fushi tarazu peptide complex identifies new class of nuclear receptors

Jiho Yoo, Sunggeon Ko, Hyeyon Kim, Heidi Sampson, Ji Hye Yun, Kwang-Min Choe, Iksoo Chang, Cheryl H. Arrowsmith, Henry M. Krause, Hyun Soo Cho, Weon Tae Lee

Research output: Contribution to journalArticle

12 Citations (Scopus)

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-F1LBDis 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.

Original languageEnglish
Pages (from-to)31225-31231
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number36
DOIs
Publication statusPublished - 2011 Sep 9

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Cytoplasmic and Nuclear Receptors
Crystal structure
Ligands
Peptides
Orphan Nuclear Receptors
Mutagenesis
Crystallography
Liver
Drosophila
Assays
Embryonic Structures
X-Rays
X rays
Molecules
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yoo, Jiho ; Ko, Sunggeon ; Kim, Hyeyon ; Sampson, Heidi ; Yun, Ji Hye ; Choe, Kwang-Min ; Chang, Iksoo ; Arrowsmith, Cheryl H. ; Krause, Henry M. ; Cho, Hyun Soo ; Lee, Weon Tae. / Crystal structure of Fushi tarazu factor 1 ligand binding domain/Fushi tarazu peptide complex identifies new class of nuclear receptors. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 36. pp. 31225-31231.
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Crystal structure of Fushi tarazu factor 1 ligand binding domain/Fushi tarazu peptide complex identifies new class of nuclear receptors. / Yoo, Jiho; Ko, Sunggeon; Kim, Hyeyon; Sampson, Heidi; Yun, Ji Hye; Choe, Kwang-Min; Chang, Iksoo; Arrowsmith, Cheryl H.; Krause, Henry M.; Cho, Hyun Soo; Lee, Weon Tae.

In: Journal of Biological Chemistry, Vol. 286, No. 36, 09.09.2011, p. 31225-31231.

Research output: Contribution to journalArticle

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AU - Cho, Hyun Soo

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