Crystal structure of the nuclear matrix targeting signal of the transcription factor acute myelogenous leukemia-1/polyoma enhancer-binding protein 2 alpha B/core binding factor alpha 2

Transcription factors of the acute myelogenous leukemia (AML)/polyoma enhan cer-binding protein (PEBP2 alpha)/core-binding factor alpha (CBFA) class ar e key transactivators of tissue-specific genes of the hematopoietic and bon e lineages. AML-1/PEBP2 alpha B/CBFA2 proteins participating in transcripti on are associated with the nuclear matrix, This association is solely depen dent on a highly conserved C-terminal protein segment, designated the nucle ar matrix targeting signal (NMTS). The NMTS of AML-1 is physically distinct from the nuclear localization signal, operates autonomously, and supports transactivation. Our data indicate that the related AML-3 and AML-2 protein s are also targeted to the nuclear matrix in situ by analogous C-terminal d omains. Here we report the first crystal structure of an NMTS in an AML-1 s egment fused to glutathione S-transferase. The model of the NMTS consists o f two loops connected by a flexible U-shaped peptide chain.