Structural Studies of the PU.1 Transcription Factor

摘要

Ets transcription factors play a role in development and are implicated in somemalignant processes. Recently, members of this large gene family have been identified in normal gene expression in mammary cells and also in breast cancer cell lines. In these studies, the crystal structure of the DNA-binding domain of the PU.1 ets protein complexed to DNA has been determined at 2.1 A resolution. The DNA binding domain is a conserved region that binds the core sequence 5'-GGAA/T-3'. The PU.1 domain binds DNA using a loop-helix-loop motif involving conserved amino acids and bases. In this project we have also used nuclear magnetic resonance (NMR) to determine the unbound structure of the domain in solution. The two structures were correlated to understand the process of DNA recognition by ets proteins.