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| - | [[Image:2h4r.gif|left|200px]]<br /><applet load="2h4r" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2h4r, resolution 2.700Å" /> | |
| - | '''Crystal structure of wildtype MENT in the native conformation'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Crystal structure of wildtype MENT in the native conformation== |
| - | 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. | + | <StructureSection load='2h4r' size='340' side='right'caption='[[2h4r]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2h4r]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H4R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H4R FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2h4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h4r OCA], [https://pdbe.org/2h4r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h4r RCSB], [https://www.ebi.ac.uk/pdbsum/2h4r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h4r ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SPB10_CHICK SPB10_CHICK] DNA-binding protein that promotes DNA condensation into transcriptionally inactive heterochromatin in terminally differentiated avian blood cells. Promotes tight packing of nucleosomes into spherical clusters by binding to linker DNA and subsequent oligomerization. Acts as a cysteine protease inhibitor towards CTSL (cathepsin L1) and CTSV (cathepsin L2), but does not inhibit serine proteases.<ref>PMID:10026180</ref> <ref>PMID:11821386</ref> <ref>PMID:12930828</ref> <ref>PMID:16810322</ref> <ref>PMID:9446625</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h4/2h4r_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2h4r ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | 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. |
| | | | |
| - | ==About this Structure==
| + | X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation.,McGowan S, Buckle AM, Irving JA, Ong PC, Bashtannyk-Puhalovich TA, Kan WT, Henderson KN, Bulynko YA, Popova EY, Smith AI, Bottomley SP, Rossjohn J, Grigoryev SA, Pike RN, Whisstock JC EMBO J. 2006 Jul 12;25(13):3144-55. Epub 2006 Jun 29. PMID:16810322<ref>PMID:16810322</ref> |
| - | 2H4R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H4R OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation., McGowan S, Buckle AM, Irving JA, Ong PC, Bashtannyk-Puhalovich TA, Kan WT, Henderson KN, Bulynko YA, Popova EY, Smith AI, Bottomley SP, Rossjohn J, Grigoryev SA, Pike RN, Whisstock JC, EMBO J. 2006 Jul 12;25(13):3144-55. Epub 2006 Jun 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16810322 16810322]
| + | </div> |
| | + | <div class="pdbe-citations 2h4r" style="background-color:#fffaf0;"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Gallus gallus]] | | [[Category: Gallus gallus]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Buckle, A.M.]] | + | [[Category: Buckle AM]] |
| - | [[Category: Irving, J.A.]] | + | [[Category: Irving JA]] |
| - | [[Category: McGowan, S.]] | + | [[Category: McGowan S]] |
| - | [[Category: Whisstock, J.C.]] | + | [[Category: Whisstock JC]] |
| - | [[Category: serine protease inhibitor]]
| + | |
| - | [[Category: serpin]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 20:14:24 2008''
| + | |
| Structural highlights
Function
SPB10_CHICK DNA-binding protein that promotes DNA condensation into transcriptionally inactive heterochromatin in terminally differentiated avian blood cells. Promotes tight packing of nucleosomes into spherical clusters by binding to linker DNA and subsequent oligomerization. Acts as a cysteine protease inhibitor towards CTSL (cathepsin L1) and CTSV (cathepsin L2), but does not inhibit serine proteases.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation.,McGowan S, Buckle AM, Irving JA, Ong PC, Bashtannyk-Puhalovich TA, Kan WT, Henderson KN, Bulynko YA, Popova EY, Smith AI, Bottomley SP, Rossjohn J, Grigoryev SA, Pike RN, Whisstock JC EMBO J. 2006 Jul 12;25(13):3144-55. Epub 2006 Jun 29. PMID:16810322[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Grigoryev SA, Bednar J, Woodcock CL. MENT, a heterochromatin protein that mediates higher order chromatin folding, is a new serpin family member. J Biol Chem. 1999 Feb 26;274(9):5626-36. PMID:10026180
- ↑ Irving JA, Shushanov SS, Pike RN, Popova EY, Bromme D, Coetzer TH, Bottomley SP, Boulynko IA, Grigoryev SA, Whisstock JC. Inhibitory activity of a heterochromatin-associated serpin (MENT) against papain-like cysteine proteinases affects chromatin structure and blocks cell proliferation. J Biol Chem. 2002 Apr 12;277(15):13192-201. Epub 2002 Jan 30. PMID:11821386 doi:http://dx.doi.org/10.1074/jbc.M108460200
- ↑ Springhetti EM, Istomina NE, Whisstock JC, Nikitina T, Woodcock CL, Grigoryev SA. Role of the M-loop and reactive center loop domains in the folding and bridging of nucleosome arrays by MENT. J Biol Chem. 2003 Oct 31;278(44):43384-93. Epub 2003 Aug 19. PMID:12930828 doi:http://dx.doi.org/10.1074/jbc.M307635200
- ↑ McGowan S, Buckle AM, Irving JA, Ong PC, Bashtannyk-Puhalovich TA, Kan WT, Henderson KN, Bulynko YA, Popova EY, Smith AI, Bottomley SP, Rossjohn J, Grigoryev SA, Pike RN, Whisstock JC. X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation. EMBO J. 2006 Jul 12;25(13):3144-55. Epub 2006 Jun 29. PMID:16810322
- ↑ Grigoryev SA, Woodcock CL. Chromatin structure in granulocytes. A link between tight compaction and accumulation of a heterochromatin-associated protein (MENT). J Biol Chem. 1998 Jan 30;273(5):3082-9. PMID:9446625
- ↑ McGowan S, Buckle AM, Irving JA, Ong PC, Bashtannyk-Puhalovich TA, Kan WT, Henderson KN, Bulynko YA, Popova EY, Smith AI, Bottomley SP, Rossjohn J, Grigoryev SA, Pike RN, Whisstock JC. X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation. EMBO J. 2006 Jul 12;25(13):3144-55. Epub 2006 Jun 29. PMID:16810322
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