Sequence-specific deoxyribonucleic acid (DNA) recognition by steroidogenic factor 1: A helix at the carboxy terminus of the DNA binding domain is necessary for complex stability

Tanya H. Little, Yongbo Zhang, Christina K. Matulis, Jennifer Weck, Zhipeng Zhang, Aparna Ramachandran, Kelly E. Mayo, Ishwar Radhakrishnan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Steroidogenic factor 1 (SF1) is a member of the NR5A subfamily of nuclear hormone receptors and is considered a master regulator of reproduction because it regulates a number of genes encoding reproductive hormones and enzymes involved in steroid hormone biosynthesis. Like other NR5A members, SF1 harbors a highly conserved approximately 30-residue segment called the FTZ-F1 box C-terminal to the core DNA binding domain (DBD) common to all nuclear receptors and binds to 9-bp DNA sequences as a monomer. Here we describe the solution structure of the SF1 DBD in complex with an atypical sequence in the proximal promoter region of the inhibin-α gene that encodes a subunit of a reproductive hormone. SF1 forms a specific complex with the DNA through a bipartite motif binding to the major and minor grooves through the core DBD and the N-terminal segment of the FTZ-F1 box, respectively, in a manner previously described for two other monomeric receptors, nerve growth factor-induced-B and estrogen-related receptor 2. However, unlike these receptors, SF1 harbors a helix in the C-terminal segment of the FTZ-F1 box that interacts with both the core DBD and DNA and serves as an important determinant of stability of the complex. We propose that the FTZ-F1 helix along with the core DBD serves as a platform for interactions with coactivators and other DNA-bound factors in the vicinity.

Original languageEnglish (US)
Pages (from-to)831-843
Number of pages13
JournalMolecular Endocrinology
Volume20
Issue number4
DOIs
StatePublished - Apr 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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