PDBsum entry: 1ttu

Transcription

PDB id: 1ttu

Contents

Protein chain

435 a.a. *

DNA/RNA

Ligands

EDO ×9

Waters ×46

* Residue conservation analysis

PDB id:

1ttu

Name:

Transcription

Title:

Crystal structure of csl bound to DNA

Structure:

5'- d( Tp Tp Ap Cp Tp Gp Tp Gp Gp Gp Ap Ap Ap Gp A)-3'. Chain: b. Engineered: yes. 5'- d( Ap Ap Tp Cp Tp Tp Tp Cp Cp Cp Ap Cp Ap Gp T)-3'. Chain: c. Engineered: yes. Lin-12 and glp-1 transcriptional regulator.

Source:

Synthetic: yes. Other_details: the sequence comes from a region within the mammalian hes-1 promoter. Caenorhabditis elegans. Organism_taxid: 6239. Gene: lag-1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Trimer (from PQS)

Resolution:

2.85Å R-factor: 0.201 R-free: 0.273

Authors:

R.A.Kovall,W.A.Hendrickson

Key ref:

R.A.Kovall and W.A.Hendrickson (2004). Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA. EMBO J, 23, 3441-3451. PubMed id: 15297877 DOI: 10.1038/sj.emboj.7600349

Date:

23-Jun-04 Release date: 31-Aug-04

Protein chain

Q9TYY1  (Q9TYY1_CAEEL) -

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (1 term)
• Biological process: regulation of transcription, DNA-dependent (1 term)
• Biochemical function: protein binding (3 terms)

DOI no: 10.1038/sj.emboj.7600349

EMBO J 23:3441-3451 (2004)

PubMed id: 15297877

Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA.

R.A.Kovall, W.A.Hendrickson.

ABSTRACT

Notch signaling is a conserved pathway of communication between neighboring cells that results in cell fate specification, and CSL is the universal transcriptional effector of Notch signaling. The Notch intracellular domain translocates to the nucleus after proteolytic release upon Notch extracellular engagement, and there it displaces corepressors from DNA-bound CSL and recruits activators of Notch target genes. Here we report the 2.85 A crystal structure of CSL with a target DNA. CSL comprises three structurally integrated domains: its amino (NTD)- and carboxy (CTD)-terminal domains are strikingly similar to those of Rel transcription factors, but a surprising beta-trefoil domain (BTD) is inserted between them. CSL-bound DNA is recognized specifically by conserved residues from NTD and BTD. A hydrophobic pocket on BTD is identified as the likely site of Notch interaction with CSL, which has functional implications for the mechanism of Notch signaling.

Selected figure(s)

Figure 4.
Figure 4 Arrangement of CTD and RHR-C with respect to NTD and RHR-N. The orientation of CTD and RHR-C in relation to NTD and RHR-N and DNA were compared for CSL and Rel proteins. The NFAT/Fos-Jun/DNA (1A02) structure is depicted on the left, the p52 homodimer -DNA structure (1A3Q) is displayed on the right, and the CSL -DNA structure is in the middle. In each case, RHR-N or NTD is colored blue and RHR-C or CTD is orange. For the comparison, the NFAT and p52 RHR-N domains were overlaid with the NTD of CSL. The p52 protomer that is not used for the overlay is lightly shaded. The orientation of RHR-N and NTD with respect to the DNA is similar in all cases; however, the resulting orientation of the RHR-C domain is different in all three examples, and unlike the RHR-C domains of NFAT and p52, the CSL CTD does not contact DNA, nor is it involved in any protein -protein interactions that promote dimerization. The figure was created with Molscript and Povscript (Kraulis, 1991; Fenn et al, 2003).

Figure 7.
Figure 7 CSL -DNA interactions. (B -D) were created with Molscript and Povscript (Kraulis, 1991; Fenn et al, 2003). (A) Schematic representation of all protein -DNA interactions in the CSL -DNA complex. Specific interactions with the DNA bases are shaded in gray and nonspecific interactions are clear boxes. Hydrogen-bonding or salt-bridge interactions are denoted as an arrow and Van der Waals interactions are depicted as closed circles. (B) Stereo view of the major-groove protein -DNA interactions of Arg234 and Asn26 from CSL with Gua8 and Gua9. The DNA is colored atom-specifically: C yellow, N blue, O red, and P gray. The protein is colored blue with interacting loops solid and other parts transparent. (C) Stereo view of the interaction of Lys368 with Gua10 and Thy7'. Coloring is as in (B). (D) Stereo view of the minor-groove interactions of the side chain of Gln401 with Ade13' and the backbone carbonyl of Ser400 with Gua6. Coloring is as in (B).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2004, 23, 3441-3451) copyright 2004.

Figures were selected by the author.