X-ray crystal structure of MENT: evidence for functional loop–sheet polymers in chromatin condensation Academic Article uri icon

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

  • 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

publication date

  • July 12, 2006