PDBsum entry 3bim

Transcription repressor

PDB id: 3bim

Contents

Protein chains

(+ 2 more) 125 a.a. *

(+ 0 more) 17 a.a. *

16 a.a. *

Waters ×141

* Residue conservation analysis

PDB id:

3bim

Name:

Transcription repressor

Title:

Crystal structure of the bcl6 btb domain dimer in complex with the bcor bbd corepressor peptide

Structure:

B-cell lymphoma 6 protein. Chain: a, b, c, d, e, f, g, h. Fragment: btb domain (also known as the poz domain). Synonym: bcl-6, zinc finger protein 51, laz-3 protein, bcl-5, zinc finger and btb domain-containing protein 27. Engineered: yes. Mutation: yes. Bcl-6 corepressor. Chain: i, j, k, l, m, n, o, p.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: bcl6, bcl5, laz3, zbtb27, znf51. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: bcor. Expression_system_taxid: 562

Resolution:

2.60Å R-factor: 0.221 R-free: 0.260

Authors:

G.G.Prive,A.F.Ghetu

Key ref:

A.F.Ghetu et al. (2008). Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer. Mol Cell, 29, 384-391. PubMed id: 18280243 DOI: 10.1016/j.molcel.2007.12.026

Date:

30-Nov-07 Release date: 08-Jan-08

Protein chains

P41182  (BCL6_HUMAN) -  B-cell lymphoma 6 protein from Homo sapiens

Seq: 706 a.a.

Struc: 125 a.a.*

Protein chains

Q6W2J9  (BCOR_HUMAN) -  BCL-6 corepressor from Homo sapiens

Seq: 1755 a.a.

Struc: 17 a.a.

Protein chains

Q6W2J9  (BCOR_HUMAN) -  BCL-6 corepressor from Homo sapiens

Seq: 1755 a.a.

Struc: 16 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, I, B, J, C, K, D, L, E, M, F, N, G, O, H, P: E.C.?

DOI no: 10.1016/j.molcel.2007.12.026

Mol Cell 29:384-391 (2008)

PubMed id: 18280243

Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer.

A.F.Ghetu, C.M.Corcoran, L.Cerchietti, V.J.Bardwell, A.Melnick, G.G.Privé.

ABSTRACT

The transcriptional corepressors BCOR, SMRT, and NCoR are known to bind competitively to the BCL6 BTB domain despite the fact that BCOR has no detectable sequence similarity to the other two corepressors. We have identified a 17 residue motif from BCOR that binds directly to the BCL6 BTB domain and determined the crystal structure of the complex to a resolution of 2.6 A. Remarkably, the BCOR BCL6 binding domain (BCOR(BBD)) peptide binds in the same BCL6 binding site as the SMRT(BBD) peptide despite the lack of any significant sequence similarity between the two peptides. Mutations of critical BCOR(BBD) residues cause the disruption of the BCL6 corepression activities of BCOR, and a BCOR(BBD) peptide blocks BCL6-mediated transcriptional repression and kills lymphoma cells.

Selected figure(s)

Figure 1.
Figure 1. Identification of the BCOR BCL6 Binding Domain
(A) BCOR fragments were purified as thioredoxin (Trx) fusion proteins and assayed for binding to the BCL6 BTB domain by native gel electrophoresis. The horizontal box indicates the position of unbound BCL6 BTB. BCL6^BTB was loaded alone (lane “−”) or as a mixture with the Trx-BCOR fragments described in (B). Equal amounts of BCL6^BTB were loaded in all lanes.
(B) Schematic of the long-isoform BCOR protein, indicating the fragments used in the binding assay in (A).
(C) Crystal structure of the BCL6^BTB/BCOR^BBD complex. The BCL6^BTB dimer is shown in cartoon representation with blue and pink subunits. The two bound BCOR^BBD peptides are shown in bond representation with green and yellow carbons, respectively.

Figure 2.
Figure 2. Comparison of the BCOR and SMRT BBD Complex Structures
(A) View of the lateral binding groove in the BCL6^BTB/BCOR^BBD complex. The BTB dimers are shown as solvent-accessible surfaces with subunit coloring as in Figure 1C. The asterisk indicates the position of residue H116 from BCL6, which is buried beneath the BBD.
(B) Superposition of the BCOR^BBD (green) and SMRT^BBD (red) peptides, represented as Cα traces with added Cβ positions. The boxed region indicates BCOR residues A505–S508 and SMRT residues G1422–I1425, in which the BBDs adopt significantly different conformations.
(C) The BCL6^BTB/SMRT^BBD complex (Ahmad et al., 2003). In this case, BCL6 residue H116 (asterisk) covers SMRT^BBD residues I1425 and S1424.
(D) Expanded view of the central region of the superposed BCOR and SMRT BBDs.
(E) Structure-based sequence alignment of the BCOR and SMRT BBDs. Gray shading indicates the four residues that form similar side-chain contacts with the BCL6 BTB domain. These are the only positions with sequence similarity (I/V; W/H) or identity (Pro) between the BCOR and SMRT BBDs. The graph shows the variation in the average Cα position between the BCOR and SMRT peptides. The error bars are the standard deviation (SD) of the 16 independent measured distances, based on two independent SMRT and eight independent BCOR crystallographic observations of the peptide structures.

The above figures are reprinted from an Open Access publication published by Cell Press: Mol Cell (2008, 29, 384-391) copyright 2008.

Figures were selected by the author.