STRUCTURES OF SAP-1 BOUND TO DNA TARGETS FROM THE E74 AND C-FOS PROMOTERS - INSIGHTS INTO DNA-SEQUENCE DISCRIMINATION BY ETS PROTEINS

SAP-1 is a member of the Ets transcription factors and cooperates with SRF protein to activate transcription of the c-fos protooncogene. The crystal structures of the conserved ETS domain of SAP-1 bound to DNA sequences from the E74 and c-fos promoters reveal that a set of conser ved residues contact a GGA core DNA sequence. Discrimination for seque nces outside this core is mediated by DNA contacts from conserved and nonconserved protein residues and sequence-dependent DNA structural pr operties characteristic of A-form DNA structure. Comparison with the r elated PU.1/DNA and GABP alpha/beta/DNA complexes provides general ins ights into DNA discrimination between Ets proteins. Modeling studies o f a SAP-1/SRF/DNA complex suggest that SRF may modulate SAP-1 binding to DNA by interacting with its ETS domain.