Cooper, Christopher D.O., Newman, Joseph A. and Gileadi, Opher (2014) Recent advances in the structural molecular biology of Ets transcription factors: interactions, interfaces and inhibition. Biochemical Society Transactions, 42 (1). pp. 130-138. ISSN 0300-5127 (print), 1470-8752 (electronic)
Abstract

The Ets family of eukaryotic transcription factors is based around the conserved Ets DNA-binding domain. Although their DNA-binding selectivity is biochemically and structurally well characterized, structures of homodimeric and ternary complexes point to Ets domains functioning as versatile protein-interaction modules. In the present paper, we review the progress made over the last decade to elucidate the structural mechanisms involved in modulation of DNA binding and protein partner selection during dimerization. We see that Ets domains, although conserved around a core architecture, have evolved to utilize a variety of interaction surfaces and binding mechanisms, reflecting Ets domains as dynamic interfaces for both DNA and protein interaction. Furthermore, we discuss recent advances in drug development for inhibition of Ets factors, and the roles structural biology can play in their future.

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