2FF0

Solution Structure of Steroidogenic Factor 1 DNA Binding Domain Bound to its Target Sequence in the Inhibin alpha-subunit Promoter

Summary for 2FF0

• Entry DOI: 10.2210/pdb2ff0/pdb
• Descriptor: GGCTCAGGGCCACAG, CTGTGGCCCTGAGCC, Steroidogenic factor 1, ... (4 entities in total)
• Functional Keywords: nuclear hormone receptor, protein-dna complex, monomeric receptor-dna complex, hormone-growth factor-dna complex, hormone/growth factor/dna
• Biological source: Mus musculus (house mouse); More
• Cellular location: Nucleus: P33242
• Total number of polymer chains: 3
• Total formula weight: 21203.72

Authors

Little, T.H.,Zhang, Y.,Matulis, C.K.,Weck, J.,Zhang, Z.,Ramachandran, A.,Mayo, K.E.,Radhakrishnan, I. (deposition date: 2005-12-17, release date: 2006-04-11, Last modification date: 2024-05-29)

Primary citation

Little, T.H.,Zhang, Y.,Matulis, C.K.,Weck, J.,Zhang, Z.,Ramachandran, A.,Mayo, K.E.,Radhakrishnan, I.
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.
Mol.Endocrinol., 20:831-843, 2006

PubMed 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-alpha 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.

PubMed: 16339274
DOI: 10.1210/me.2005-0384

Experimental method

SOLUTION NMR