title: X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Sheena
authors.initials: S
authors.lastname: McGowan
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Buckle
authors.forename: James A
authors.initials: JA
authors.lastname: Irving
authors.forename: Poh Chee
authors.initials: PC
authors.lastname: Ong
authors.forename: Tanya A
authors.initials: TA
authors.lastname: Bashtannyk-Puhalovich
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Kan
authors.forename: Kate N
authors.initials: KN
authors.lastname: Henderson
authors.forename: Yaroslava A
authors.initials: YA
authors.lastname: Bulynko
authors.forename: Evgenya Y
authors.initials: EY
authors.lastname: Popova
authors.forename: A Ian
authors.initials: AI
authors.lastname: Smith
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Bottomley
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Grigoryev
authors.forename: Robert N
authors.initials: RN
authors.lastname: Pike
authors.forename: James C
authors.initials: JC
authors.lastname: Whisstock
mesh_terms: D000818:Animals; D001665:Binding Sites; D056668:Cathepsin L; D002403:Cathepsins / Q000737:chemistry; D002843:Chromatin / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism; D011487:Protein Conformation; D015843:Serpins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D015843:Serpins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L