Question

Structures of all three repeats (R1, R2 and R3) of c-Myb protein are similar but their thermal stability differs. Why is this important?

Answer 1

Structures of all three repeats (R1, R2 and R3) of c-Myb protein are similar but their thermal stability differs. Why is this important?

The c-myb proto-oncogene product (c-Myb) is an essential regulator of proliferation and differentiation of hematopoietic cells (Lipsick and Wang, 1999). c-Myb goes about as a transcriptional administrative factor (Weston and Bishop 1989, Ness et al. 1989, Sakura et al. 1989), balancing articulation of different target qualities in the hematopoietic framework, much of the time with collaboration of a wide assortment of other transcriptional administrative elements, including individuals from the CAAT-enhancer restricting protein (C/EBP) family, the Ets family, and center restricting components (CBFs) (Ness, 1999). Specifically, C/EBP relatives (C/EBPα, C/EBPβ, C/EBPδ, and C/EBPϵ) are much of the time watched and all around portrayed c-Myb accomplices, controlling interpretation of such hematopoietic qualities as mim-1 (Ness et al. 1993, Burk et al. 1993), lysozyme (Ness et al., 1993), tom-1A (Burk et al., 1997), myeloperoxidase (MPO) (Bristos-Bray and Friedman, 1997), neutrophil elastase (Oelgeschläger et al. 1996, Verbeek et al. 1999), RAG2 (Fong et al., 2000), and myeloblastin (Lutz et al., 2001). Without a doubt, ectopic articulation of Myb and C/EBPs in heterologous cell types incites endogenous markers of myeloid separation, including mim-1 and lysozyme qualities (Ness et al., 1993).

The DBD of c-Myb consists of three imperfect tandem repeats of 51 or 52 amino acid residues, referred to as R1, R2, and R3 from the N terminus (Kanei-Ishii et al., 1990). Our past investigations of the structures in arrangement utilizing atomic attractive reverberation (NMR) spectroscopy uncovered that each rehash contains three helices (α1, α2, and α3) with the helix-turn-helix variation theme (Ogata et al. 1992, Ogata et al. 1995), and that R2 and R3 are associated with particular DNA acknowledgment, while R1 freely covers the DNA position alongside the R2 restricting site (Ogata et al. 1994, Ogata et al. 1995). The structure of R2 additionally contains a somewhat uncovered hydrophobic fix (Ogata et al., 1995); inside the relating locale of the AMV v-Myb DBD, this hydrophobic fix contains the three point changes in charge of the disappointment of v-Myb to enact the mim-1 advertiser (Ness et al. 1989, Introna et al. 1990, Ogata et al. 1995, Kowenz-Leutz et al. 1997), recommending that this hydrophobic fix is critical for the connection of c-Myb and C/EBPβ and for their synergistic initiation of interpretation.

To establish the structural basis for the synergy between c-Myb and C/EBPβ and its disruption by the mutations found in the AMV v-Myb DBD, we determined the crystal structures of ternary complexes containing the c-Myb or AMV v-Myb DBD, the C-terminal portion of C/EBPβ, including the DBD, and a DNA fragment from the tom-1A promoter: c-Myb_38-193–C/EBPβ_259-336–DNA, c-Myb_38-193–C/EBPβ_273-336–DNA, and AMV v-Myb_66-193–C/EBPβ_259-336–DNA are respectively named c-Myb complex I, c-Myb complex II (or generally c-Myb complex without discrimination of complexes I and II).