A pivot-tether model for nucleosome recognition by the chromosomal passenger complex.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-07-15 DOI:10.1038/s44319-025-00523-4

Reinis R Ruza, Chyi Wei Chung, Danny B H Gold, Michela Serena, Emile Roberts, Ulrike Gruneberg, Francis A Barr

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Abstract

Spatial restriction of Aurora B to T3-phosphorylated histone H3 (H3pT3) nucleosomes adjacent to centromeres during prometaphase and metaphase enables it to phosphorylate proteins necessary for spindle assembly checkpoint signalling and biorientation of chromosomes on the mitotic spindle. Aurora B binding to H3pT3-nucleosomes requires a multivalent targeting module, the chromosomal passenger complex (CPC), consisting of survivin, borealin, and INCENP. To shed light on how these components mediate CPC localisation during prometaphase and metaphase, we determined the structure of the CPC targeting module in complex with haspin-phosphorylated H3pT3-nucleosomes by cryo-electron microscopy. This structure shows how the N-terminus of borealin and the survivin BIR domain act as pivot and flexible tethering points, respectively, to increase CPC affinity for H3pT3 nucleosomes without limiting it to a specific orientation. We demonstrate that this flexible, yet constrained pivot-tether arrangement is important for the control of spindle assembly checkpoint signalling by Aurora B.

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染色体乘客复合体识别核小体的枢轴-系绳模型。

在前期和中期，Aurora B对靠近着丝粒的t3磷酸化组蛋白H3 （H3pT3）核小体的空间限制使其能够磷酸化纺锤体组装检查点信号和有丝分裂纺锤体上染色体的双向定位所必需的蛋白质。Aurora B与h3pt3核小体的结合需要一个多价靶向模块，即染色体乘客复合物（CPC），由survivin、borealin和INCENP组成。为了阐明这些成分是如何在前期和中期介导CPC定位的，我们通过冷冻电镜确定了CPC靶向模块与haspin磷酸化的h3pt3核小体复合物的结构。该结构显示了borealin的n端和survivin BIR结构域如何分别作为支点和灵活的系聚点，以增加CPC对H3pT3核小体的亲和力，而不将其限制在特定的方向上。我们证明，这种灵活的，但约束轴系绳安排是重要的控制主轴装配检查点信号的极光B。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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