Optical spectroscopy investigation of peptides issued from the AML1-ETO–E-protein complex relevant to acute myeloid leukemia

Abstract

The expression of AML1-ETO, resulting from the t(8; 21) chromosomal translocation causes 15% of acute myeloid leukaemias. The region of ETO, bearing the motif LxxLL, is involved in the oligomerisation of the AML1-ETO. Peptide NHR2 is one of the objects of the present investigation. The region of ETO may recruit AML1-ETO to transcription activators, such as E-protein. Peptide TAFH is another object of the present investigation. interacts with E-protein through the domain of the latter, which possesses an LxxLL motif as well. Peptide AD1 is the third object of the present investigation. By CD, ANS fluorescence and intrinsic fluorescence, we suggest an antiparallel coiled-coil encounter of two molecules (Kd = 2.8-4 µM) as a prerequisite to tetramer formation. On the other hand, we show that the domain would probably recognize another partner bearing the LxxLL motif and, before binding to (Kd = 28 nM), the first such interaction is likely to be intramolecular, with the domain of the AML1-ETO protein itself (Kd = 1.28 nM). Furthermore, a possible interaction of with is also revealed (Kd = 240 nM). The biological implications of the results are discussed.