Sequence-Specific DNA Recognition by Steroidogenic Factor 1: A Helix at the Carboxy-Terminus of the DNA Binding Domain is Necessary for Complex Stability

Abbreviated title: Structure-Function of SF1-DNA Interactions Key words: SF1; nuclear hormone receptor; DNA recognition; NMR; solution structure Disclosure of Potential Conflicts of Interest: K.E.M. has consulted for World Book Science Inc., has equity interests in Ligand Pharmaceuticals Inc., and received lecture fees from Serono Inc., but has no conflicts with entities directly related to the material being published. All other authors have nothing to disclose. This is an un-copyedited author manuscript copyrighted by The Endocrine Society. This may not be duplicated or reproduced, other than for personal use or within the rule of "Fair Use of Copyrighted Materials" (section 107, Title 17, U.S. Code) without permission of the copyright owner, The Endocrine Society. From the time of acceptance following peer review, the full text of this manuscript is made freely available by The Endocrine Society at http://www.endojournals.org/. The final copy edited article can be found at http://www.endojournals.org/. The Endocrine Society disclaims any responsibility or liability for errors or omissions in this version of the manuscript or in any version derived from it by the National Institutes of Health or other parties. base-pair 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 inhibingene 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, NGFI-B and ERR2. 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.