Article
- The EMBO Journal (2006) 25, 3144 - 3155
- doi:10.1038/sj.emboj.7601201
Published online: 29 June 2006
Subject Categories:
X-ray crystal structure of MENT: evidence for functional loop–sheet polymers in chromatin condensation
Sheena McGowan1,a, Ashley M Buckle1,a, James A Irving1,a, Poh Chee Ong1,a, Tanya A Bashtannyk-Puhalovich1, Wan-Ting Kan1, Kate N Henderson1, Yaroslava A Bulynko2, Evgenya Y Popova2, A Ian Smith1, Stephen P Bottomley1, Jamie Rossjohn1, Sergei A Grigoryev2, Robert N Pike1,3 and James C Whisstock1,3
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
- Department of Biochemistry and Molecular Biology, Penn State University College of Medicine, Milton S Hershey Medical Center, Hershey, PA, USA
- Joint senior authors
Correspondence to:
James C Whisstock, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. Tel.: +613 9905 3747; Fax: +613 9905 4699; E-mail: James.Whisstock@med.monash.edu.au
Sergei A Grigoryev, Department of Biochemistry and Molecular Biology, Penn State University College of Medicine, H171, Milton S Hershey Medical Center, PO Box 850, 500 University Drive, Hershey, PA 17033, USA. Tel.: +1 717 531 8588; Fax: +1 717 531 7072; E-mail: sag17@psu.edu
aThese authors contributed equally to this work
Received 9 December 2005; Accepted 22 May 2006
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.
Keywords:
- chromatin compaction,
- MENT,
- nucleosome,
- serpin
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