| 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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