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.