PDBsum entry 2h4r

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protein links
Hydrolase inhibitor PDB id
Jmol PyMol
Protein chain
371 a.a. *
Waters ×111
* Residue conservation analysis
PDB id:
Name: Hydrolase inhibitor
Title: Crystal structure of wildtype ment in the native conformatio
Structure: Heterochromatin-associated protein ment. Chain: a. Synonym: ment. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Gene: ment-1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
2.70Å     R-factor:   0.205     R-free:   0.282
Authors: J.A.Irving,J.C.Whisstock,A.M.Buckle,S.Mcgowan
Key ref:
S.McGowan et al. (2006). X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation. EMBO J, 25, 3144-3155. PubMed id: 16810322 DOI: 10.1038/sj.emboj.7601201
25-May-06     Release date:   18-Jul-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O73790  (SPB10_CHICK) -  Heterochromatin-associated protein MENT
410 a.a.
371 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   5 terms 
  Biological process     chromosome condensation   5 terms 
  Biochemical function     DNA binding     4 terms  


DOI no: 10.1038/sj.emboj.7601201 EMBO J 25:3144-3155 (2006)
PubMed id: 16810322  
X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation.
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.
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.
  Selected figure(s)  
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.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21326229 M.A.Adams-Cioaba, J.C.Krupa, C.Xu, J.S.Mort, and J.Min (2011).
Structural basis for the recognition and cleavage of histone H3 by cathepsin L.
  Nat Commun, 2, 197.
PDB codes: 3iv2 3k24
20731544 J.A.Huntington, and J.C.Whisstock (2010).
Molecular contortionism - on the physical limits of serpin 'loop-sheet' polymers.
  Biol Chem, 391, 973-982.  
21081089 S.Ricagno, M.Pezzullo, A.Barbiroli, M.Manno, M.Levantino, M.G.Santangelo, F.Bonomi, and M.Bolognesi (2010).
Two latent and two hyperstable polymeric forms of human neuroserpin.
  Biophys J, 99, 3402-3411.  
19245336 B.Gooptu, and D.A.Lomas (2009).
Conformational pathology of the serpins: themes, variations, and therapeutic strategies.
  Annu Rev Biochem, 78, 147-176.  
19232354 B.Gooptu, E.Miranda, I.Nobeli, M.Mallya, A.Purkiss, S.C.Brown, C.Summers, R.L.Phillips, D.A.Lomas, and T.E.Barrett (2009).
Crystallographic and cellular characterisation of two mechanisms stabilising the native fold of alpha1-antitrypsin: implications for disease and drug design.
  J Mol Biol, 387, 857-868.
PDB codes: 3drm 3dru
19266095 P.C.Ong, S.J.Golding, M.C.Pearce, J.A.Irving, S.A.Grigoryev, D.Pike, C.G.Langendorf, T.A.Bashtannyk-Puhalovich, S.P.Bottomley, J.C.Whisstock, R.N.Pike, and S.McGowan (2009).
Conformational change in the chromatin remodelling protein MENT.
  PLoS ONE, 4, e4727.  
19522701 T.A.Murray-Rust, F.K.Kerr, A.R.Thomas, T.Wu, T.Yongqing, P.C.Ong, N.S.Quinsey, J.C.Whisstock, I.C.Wagenaar-Bos, C.Freeman, and R.N.Pike (2009).
Modulation of the proteolytic activity of the complement protease C1s by polyanions: implications for polyanion-mediated acceleration of interaction between C1s and SERPING1.
  Biochem J, 422, 295-303.  
18468442 J.Zlatanova, C.Seebart, and M.Tomschik (2008).
The linker-protein network: control of nucleosomal DNA accessibility.
  Trends Biochem Sci, 33, 247-253.  
18063751 R.H.Law, T.Sofian, W.T.Kan, A.J.Horvath, C.R.Hitchen, C.G.Langendorf, A.M.Buckle, J.C.Whisstock, and P.B.Coughlin (2008).
X-ray crystal structure of the fibrinolysis inhibitor alpha2-antiplasmin.
  Blood, 111, 2049-2052.
PDB code: 2r9y
18436534 S.H.Li, N.V.Gorlatova, D.A.Lawrence, and B.S.Schwartz (2008).
Structural differences between active forms of plasminogen activator inhibitor type 1 revealed by conformationally sensitive ligands.
  J Biol Chem, 283, 18147-18157.  
18362167 S.J.McBryant, C.Krause, C.L.Woodcock, and J.C.Hansen (2008).
The silent information regulator 3 protein, SIR3p, binds to chromatin fibers and assembles a hypercondensed chromatin architecture in the presence of salt.
  Mol Cell Biol, 28, 3563-3572.  
18060440 T.H.Roberts, and J.Hejgaard (2008).
Serpins in plants and green algae.
  Funct Integr Genomics, 8, 1.  
17923478 P.C.Ong, S.McGowan, M.C.Pearce, J.A.Irving, W.T.Kan, S.A.Grigoryev, B.Turk, G.A.Silverman, K.Brix, S.P.Bottomley, J.C.Whisstock, and R.N.Pike (2007).
DNA accelerates the inhibition of human cathepsin v by serpins.
  J Biol Chem, 282, 36980-36986.  
17660293 T.Nikitina, R.P.Ghosh, R.A.Horowitz-Scherer, J.C.Hansen, S.A.Grigoryev, and C.L.Woodcock (2007).
MeCP2-chromatin interactions include the formation of chromatosome-like structures and are altered in mutations causing Rett syndrome.
  J Biol Chem, 282, 28237-28245.  
17079131 J.C.Whisstock, and S.P.Bottomley (2006).
Molecular gymnastics: serpin structure, folding and misfolding.
  Curr Opin Struct Biol, 16, 761-768.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.