X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation. (2H4R)

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.

大多数丝氨酸蛋白酶抑制剂（serpins）与蛋白酶抑制相关，其形成环-片聚合物的能力与构象病及人类丝氨酸蛋白酶抑制剂病（serpinopathies）密切相关。本文阐述了一种独特的丝氨酸蛋白酶抑制剂——非组蛋白结构蛋白MENT（髓系与红系细胞核终末阶段特异性蛋白）参与DNA及染色质压缩的结构与功能解析。我们的数据表明，MENT包含至少两个不同的DNA结合位点，这与其同时结合核小体上两个紧密相邻的连接DNA片段的特性一致。值得注意的是，我们的研究发现，反应中心环（MENT分子中在体内外染色质桥接过程中不可或缺的区域）能够介导环-片寡聚物的形成。这些数据为理解非组蛋白结构蛋白介导的染色质压缩机制提供了深入见解，并揭示了丝氨酸蛋白酶抑制剂的结构可塑性如何演化以介导生理性而非致病性的环-片连接。