 |
PDBsum entry 3bim
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transcription repressor
|
PDB id
|
|
|
|
3bim
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
(+ 2 more)
125 a.a.
|
|
|
|
|
|
|
|
|
|
|
(+ 0 more)
17 a.a.
|
|
|
|
|
|
|
|
|
|
|
16 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of a bcor corepressor peptide in complex with the bcl6 btb domain dimer.
|
|
|
Authors
|
|
A.F.Ghetu,
C.M.Corcoran,
L.Cerchietti,
V.J.Bardwell,
A.Melnick,
G.G.Privé.
|
|
|
Ref.
|
|
Mol Cell, 2008,
29,
384-391.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
