Sequence and structure of ELF-1 dominant-negative peptides. (A) Protein sequence of the Ets domain of ELF-1. Red boxes demonstrate amino acids altered in mutant peptide to block binding. Amino acid sequences spanned by peptides A through E are highlighted above the sequence and alpha and beta helical structural components of the DNA binding domain are denoted below the sequence. (B) Structural model illustrating the critical secondary structural elements of ETS domains, using the crystal structure of the Ets-1 DNA binding domain in complex with duplex DNA, 5′-GGAA-3′ solved to a resolution of 0.24 nm (2.4 Å). The 5 α-helices are colored red and labeled H1 to H5, the turns and loops of the ETS domain are green, the antiparallel β sheet is colored yellow, and the DNA is rendered in black using InsightII (Accelrys, San Diego, CA). (i) Peptide A is 34 amino acids in length and is composed of the H3 recognition helix, which possesses 3 amino acids that contact the core of the DNA duplex with a set of highly conserved base contacts illustrated in blue. (ii) Peptide B includes most of the recognition helix and encompasses these 3 critical residues but does not include the remainder of the canonical ETS anchor that is composed of several loops or “wings” that are responsible for minor groove DNA contacts. (iii-v) Peptides C through E are composed of other ETS structural elements but lack the H3 recognition helix and/or the 3 critical residues that are responsible for anchoring the ETS domain within the major groove.