SANS characterization of the transcription factors Pbx1and Prep 1 in complex with DNA
Homeodomain (HD) transcription factors include the Pbx, Prep and Hox families, which are involved in human cancer (1). The aim of this project is to characterize the structure of the tumor suppressor protein Prep1 (2) in complex with its binding partner Pbx1, and to clarify their interaction with DNA. The mechanism of interactions between Pbx1 and Prep1 will be uncovered and the structure of the heterodimer bound to DNA will allow us to gain insights into the DNA target specificity and binding properties of the Prep1–Pbx1 heterodimer. We have done SANS measurements on December 2011 at ILL but data were inconclusive, due to the too low concentration of the complex. HD proteins are difficult to crystallize in their full length, and then we believe that SANS data of the Prep1-Pbx1 complex are essential to unravel their binding mode to DNA. Furthermore we are proposing to investigate the Prep1- Pbx1-HoxB1 HDs all assembled on DNA. By selective deuteration of Prep1 HD, we are actually willing to solvent match all the components of the tetrameric HD complex. (1) Wong, P., et al Genes Dev 21, 2762-74 (2007) (2) Longobardi, E. et al. Mol Oncol 4, 126-34 (2010)
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BRUCKMANN Chiara; MACCARINI Marco; MARIANI Paolo; Ortore M.G.; SCHWEINS Ralf and SPINOZZI Francesco. (2013). SANS characterization of the transcription factors Pbx1and Prep 1 in complex with DNA. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.8-03-782