 |
PDBsum entry 2h4q
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase inhibitor
|
PDB id
|
|
|
|
2h4q
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
X-Ray crystal structure of ment: evidence for functional loop-Sheet polymers in chromatin condensation.
|
|
|
Authors
|
|
S.Mcgowan,
A.M.Buckle,
J.A.Irving,
P.C.Ong,
T.A.Bashtannyk-Puhalovich,
W.T.Kan,
K.N.Henderson,
Y.A.Bulynko,
E.Y.Popova,
A.I.Smith,
S.P.Bottomley,
J.Rossjohn,
S.A.Grigoryev,
R.N.Pike,
J.C.Whisstock.
|
|
|
Ref.
|
|
EMBO J, 2006,
25,
3144-3155.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Most serpins are associated with protease inhibition, and their ability to form
loop-sheet polymers is linked to conformational disease and the human
serpinopathies. Here we describe the structural and functional dissection of how
a unique serpin, the non-histone architectural protein, MENT (Myeloid and
Erythroid Nuclear Termination stage-specific protein), participates in DNA and
chromatin condensation. Our data suggest that MENT contains at least two
distinct DNA-binding sites, consistent with its simultaneous binding to the two
closely juxtaposed linker DNA segments on a nucleosome. Remarkably, our studies
suggest that the reactive centre loop, a region of the MENT molecule essential
for chromatin bridging in vivo and in vitro, is able to mediate formation of a
loop-sheet oligomer. These data provide mechanistic insight into chromatin
compaction by a non-histone architectural protein and suggest how the structural
plasticity of serpins has adapted to mediate physiological, rather than
pathogenic, loop-sheet linkages.
|
|
|
|
|
|
|
|
Figure 5.
Figure 5 (A) The structure of cleaved MENT[WT] labelled as in
Figure 1A. The termini of the M-loop (between hC and hD) are
indicated by ^*. (B) Superposition of native (green) and cleaved
(brown) MENT[WT]. The change in conformation at the top of the
D-helix is indicated by a dotted square and shown in the inset.
Hydrogen bonds are shown by dashed lines and R109, N110, Y112,
F105 and A104 are labelled. (C) CCP4MG (Potterton et al, 2002,
2004) electrostatic potential surface of cleaved MENT[WT],
coloured as in Figure 1B.
|
|
Figure 6.
Figure 6 (A) Structure of the native MENT[  Mloop]
tetramer in the asymmetric unit. Each monomer is coloured
differently; the orange and green monomers form a 'back to back'
dimer (indicated by a dotted oval); the orange molecule forms a
loop–sheet linkage (arrow) to the cyan molecule and a
loop–sheet linkage to the magenta molecule. hD and hE are
labelled. (B) Loop–sheet hydrogen bonds formed by the RCL
(brown) of one molecule with the s6A of an adjoining molecule
(green). Hydrogen bonds are shown as magenta broken lines. (C)
Comparison of native MENT[WT] (blue) and MENT[ Mloop]
(green) reveals conformational change in the C-terminus
(labelled) and s5A/s6A of the A  -sheet
of MENT[ Mloop]
in response to the interaction with the RCL of a neighbouring
molecule (magenta). Note also the different trajectory of the
RCL (labelled).
|
|
|
|
|
|
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
EMBO J
(2006,
25,
3144-3155)
copyright 2006.
|
|
|
|
|
|
|
