X-ray crystal structure of MENT: Evidence for functional loop-sheet polymers in chromatin condensation

Sheena McGowan, Ashley M. Buckle, James A. Irving, Poh Chee Ong, Tanya A. Bashtannyk-Puhalovich, Wan Ting Kan, Kate N. Henderson, Yaroslava A. Bulynko, Evgenya Y. Popova, A. Ian Smith, Stephen P. Bottomley, Jamie Rossjohn, Sergei A. Grigoryev, Robert N. Pike, James C. Whisstock

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3144-3155
Number of pages12
JournalEMBO Journal
Volume25
Issue number13
DOIs
StatePublished - Jul 12 2006

Fingerprint

Serpins
Chromatin
Condensation
Polymers
Crystal structure
X-Rays
X rays
DNA
Dissection
Proteins
Nucleosomes
Oligomers
Plasticity
Compaction
Peptide Hydrolases
Binding Sites
Molecules

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

McGowan, S., Buckle, A. M., Irving, J. A., Ong, P. C., Bashtannyk-Puhalovich, T. A., Kan, W. T., ... Whisstock, J. C. (2006). X-ray crystal structure of MENT: Evidence for functional loop-sheet polymers in chromatin condensation. EMBO Journal, 25(13), 3144-3155. https://doi.org/10.1038/sj.emboj.7601201
McGowan, Sheena ; Buckle, Ashley M. ; Irving, James A. ; Ong, Poh Chee ; Bashtannyk-Puhalovich, Tanya A. ; Kan, Wan Ting ; Henderson, Kate N. ; Bulynko, Yaroslava A. ; Popova, Evgenya Y. ; Smith, A. Ian ; Bottomley, Stephen P. ; Rossjohn, Jamie ; Grigoryev, Sergei A. ; Pike, Robert N. ; Whisstock, James C. / X-ray crystal structure of MENT : Evidence for functional loop-sheet polymers in chromatin condensation. In: EMBO Journal. 2006 ; Vol. 25, No. 13. pp. 3144-3155.
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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 2006, 'X-ray crystal structure of MENT: Evidence for functional loop-sheet polymers in chromatin condensation', EMBO Journal, vol. 25, no. 13, pp. 3144-3155. https://doi.org/10.1038/sj.emboj.7601201

X-ray crystal structure of MENT : Evidence for functional loop-sheet polymers in chromatin condensation. / McGowan, Sheena; Buckle, Ashley M.; Irving, James A.; Ong, Poh Chee; Bashtannyk-Puhalovich, Tanya A.; Kan, Wan Ting; Henderson, Kate N.; Bulynko, Yaroslava A.; Popova, Evgenya Y.; Smith, A. Ian; Bottomley, Stephen P.; Rossjohn, Jamie; Grigoryev, Sergei A.; Pike, Robert N.; Whisstock, James C.

In: EMBO Journal, Vol. 25, No. 13, 12.07.2006, p. 3144-3155.

Research output: Contribution to journalArticle

TY - JOUR

T1 - X-ray crystal structure of MENT

T2 - Evidence for functional loop-sheet polymers in chromatin condensation

AU - McGowan, Sheena

AU - Buckle, Ashley M.

AU - Irving, James A.

AU - Ong, Poh Chee

AU - Bashtannyk-Puhalovich, Tanya A.

AU - Kan, Wan Ting

AU - Henderson, Kate N.

AU - Bulynko, Yaroslava A.

AU - Popova, Evgenya Y.

AU - Smith, A. Ian

AU - Bottomley, Stephen P.

AU - Rossjohn, Jamie

AU - Grigoryev, Sergei A.

AU - Pike, Robert N.

AU - Whisstock, James C.

PY - 2006/7/12

Y1 - 2006/7/12

N2 - 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.

AB - 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.

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McGowan S, Buckle AM, Irving JA, Ong PC, Bashtannyk-Puhalovich TA, Kan WT et al. X-ray crystal structure of MENT: Evidence for functional loop-sheet polymers in chromatin condensation. EMBO Journal. 2006 Jul 12;25(13):3144-3155. https://doi.org/10.1038/sj.emboj.7601201