The B-box dominates SAP-1-SRF interactions in the structure of the ternarycomplex

The serum response element (SRE) is found in several immediate-early gene p romoters. This DNA sequence is necessary and sufficient for rapid transcrip tional induction of the human c-fos proto-oncogene in response to stimuli e xternal to the cell. Full activation of the SRE requires the cooperative bi nding of a ternary complex factor (TCF) and serum response factor (SRF) to their specific DNA sites. The X-ray structure of the human SAP-1-SRF-SRE DN A ternary complex was determined (Protein Data Bank code 1hbx). It shows SA P-1 TCF bound to SRF through interactions between the SAP-1 B-box and SRE M ADS domain in addition to contacts between their respective DNA-binding mot ifs, The SAP-1 B-box is part of a flexible linker of which 21 amino acids b ecome ordered upon ternary complex formation. Comparison with a similar reg ion from the yeast MAT alpha2-MCM1-DNA complex suggests a common binding mo tif through which MADS-box proteins may interact with additional factors su ch as Fli-1.