PDBsum entry 1r29

Transcription

PDB id

1r29

Contents

			Protein chain

					122 a.a. *

			Waters ×188

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Mechanism of smrt corepressor recruitment by the bcl6 btb domain.

Authors

K.F.Ahmad, A.Melnick, S.Lax, D.Bouchard, J.Liu, C.L.Kiang, S.Mayer, S.Takahashi, J.D.Licht, G.G.Privé.

Ref.

Mol Cell, 2003, 12, 1551-1564. [DOI no: 10.1016/S1097-2765(03)00454-4]

PubMed id

14690607

Abstract

BCL6 encodes a transcription factor that represses genes necessary for the terminal differentiation of lymphocytes within germinal centers, and the misregulated expression of this factor is strongly implicated in several types of B cell lymphoma. The homodimeric BTB domain of BCL6 (also known as the POZ domain) is required for the repression activity of the protein and interacts directly with the SMRT and N-CoR corepressors that are found within large multiprotein histone deacetylase-containing complexes. We have identified a 17 residue fragment from SMRT that binds to the BCL6 BTB domain, and determined the crystal structure of the complex to 2.2 A. Two SMRT fragments bind symmetrically to the BCL6 BTB homodimer and, in combination with biochemical and in vivo data, the structure provides insight into the basis of transcriptional repression by this critical B cell lymphoma protein.



	Figure 3. Figure 3. Structure of the BCL6 BTB Domain/SMRT-BBD Complex(A) Ribbon diagram of the 2:2 complex. The crystallographic asymmetric unit contains the entire four-chain structure. The two chains of the BCL6 BTB domain dimer are colored blue and red, and the two SMRT chains are colored yellow and green. The N termini of the two SMRT chains are labeled.(B–D) View of the BCL6 BTB domain displayed as a solvent accessible surface colored according to the two chains of the BTB dimer (blue and white), with the two SMRT fragments rendered in stick representation (oxygens in red, nitrogens in blue, and the carbons of the two corepressor chains colored in either yellow or green, as in [A]). The two nonoverlapping surfaces of the BCL6 BTB dimer that are buried upon peptide binding are highlighted in purple. (B) View in same orientation as in [A]. (C) “Bottom” of the complex, viewed along the molecular pseudo-2-fold axis. (D) Ser-1424 (hidden by His-116 in this view) and Ile-1425 of SMRT are buried in a groove formed in part by Arg-13′ (α1′) and His-116 (α6) from the two chains of the BCL6 BTB domain.(E) Sequence alignment of selected human BTB/zinc finger proteins and the observed secondary structure of the BCL6 BTB domain. The residue-by-residue surfaces buried due to interactions with the yellow SMRT peptide are indicated with red and blue bars (color scheme according to [A]). HIC-1 has a 13 amino acid insert at the position indicated by the three asterisks.		Figure 4. Figure 4. Peptide Binding Interactions(A) Schematic drawing of the contacts between the BCL6 BTB domain and the “yellow” SMRT chain (colors as in Figure 3A). Nearly identical contacts are observed in the other contact surface.(B) Highlight of the interactions between SMRT 1427–1430 and the BCL6 BTB domain.(C) Interactions of SMRT 1424–1426 with the BCL6 BTB domain.(D) To view the interactions between region 1414–1423 of the SMRT-BBD peptide and BTB β1′, the BCL6 helix α6 (red chain) has been made transparent.(E) Superposition of the two crystallographically independent SMRT peptides from the complex, with carbons shown in yellow and green as in Figure 3. The six waters from each site that participate in the bridging SMRT/BCL6 interactions are indicated as yellow or green spheres.(F) Mutations in the BCL6 BTB peptide binding pocket reduce the affinity for the SMRT peptide. His-tagged Trx-(SMRT-BBD) was mixed with three different forms of the BCL6 BTB domain, and the load (“L”), flow through (“FT”), wash (“W”), and elute (“E”) fractions from each copurification trial were analyzed by SDS-PAGE.

PROCHECK

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