The Notch Transcription Activation Complex Makes Its Move

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The Notch Transcription Activation Complex Makes Its Move Doug Barrick, Raphael Kopan  Cell  Volume 124, Issue 5, Pages 883-885 (March 2006) DOI: 10.1016/j.cell.2006.02.028 Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 1 The Notch Transcription Activation Complex Molecular recognition and conformational changes at the switch point for Notch transcriptional activation are depicted. (A) Distant regions of the Notch intracellular domain (NICD), including the RAM (blue tube) and ANK (blue ribbons) domains, interact with distinct regions of the transcriptional repressor CSL, including the β trefoil domain (BTD, bright red), and the N- and C-terminal domains of CSL (NTD and CTD, pink and dark red, respectively) (Wilson and Kovall, 2006). DNA bound by the complex is in yellow. (B) Together with the CTD domain of CSL (red), the ANK domain of NICD (blue) forms a combined interface into which a long (∼8 turn) helix of MAM binds, much like a hot dog in a bun (Nam et al., 2006). (C) The RAM-ANK-MAM-CSL structure (right, blue) and the ANK-MAM-CSL (left, red) structure were superimposed (middle panel) to illustrate the large (∼10 Å) structural displacement in the region of the CTD of CSL coincident with the binding of RAM to BTD. This displacement (blue and red arrows to mark the CTD, yellow and green mark the distance between the BTD and CTD) is amplified into the ANK domain (pink and turquoise arrows) relative to the BTD by its entire width. Note that the contacts with DNA remain unchanged. Also, note the presence of an additional ankyrin fold in the blue structure above the turquoise arrow. The structure undergoes a ratchet motion when RAM is present. This is best seen in Movie S1 available with this article online. Still images were generated using MacPymol (http://www.pymol.org) and were superimposed using Canvas, and the movie of these images was assembled in QuickTime Pro. Cell 2006 124, 883-885DOI: (10.1016/j.cell.2006.02.028) Copyright © 2006 Elsevier Inc. Terms and Conditions