Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization.
Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization.
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DOI：
10.1016/j.molcel.2022.04.027
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发表时间：
2022-06-02
期刊：
影响因子：
16
通讯作者：
Musacchio, Andrea
中科院分区：
文献类型：
--
作者：
Pesenti, Marion E.;Raisch, Tobias;Conti, Duccio;Walstein, Kai;Hoffmann, Ingrid;Vogt, Dorothee;Prumbaum, Daniel;Vetter, Ingrid R.;Raunser, Stefan;Musacchio, Andrea
着丝粒是一种特殊的染色体位点，它为着丝点提供种子，着丝点是一种影响染色体分离的大型蛋白质复合体。一个16亚基复合物，即组成性着丝粒相关网络（CCAN），连接着特殊的着丝粒染色质（以组蛋白H3变体CENP-A为标志）和着丝粒的纺锤体结合部分。在这里，我们报告了人类CCAN的低温电镜结构。我们强调了独特的特征，如伪GTPase CENP-M，并报告了一个关键的CENP-C基序如何结合CENP-LN复合物。CCAN结构对特异性识别CENP-A核小体的机制具有启示意义。与我们的结构一致的模型描述了通过扩展的，灵活的CENP-C区域连接到CCAN的CENP-C结合核小体。另一种模型将CENP-C和CENP-N确定为特异性决定因素，但要求CENP-N以与经典核小体八聚体不同的模式结合CENP-A。报道了CCAN的低温电镜结构，该结构使16个CCAN亚基的相对位置和作用合理化，CCAN核心显示出比CENP-A核小体更倾向于裸DNA，讨论了着丝粒染色质的几种可能的组织模式。着丝粒是一个特殊的染色体位点，它为着丝粒提供种子，着丝粒是促进染色体分离的大分子复合物。Pesenti、Raisch等人报道了组成性着丝粒相关网络（CCAN）的结构，这是一个围绕着着丝粒表观遗传标记CENP-A/CenH3的多亚基组装体。这种结构对着丝粒的组织提出了根本性的新问题。
Centromeres are specialized chromosome loci that seed the kinetochore, a large protein complex that effects chromosome segregation. A 16-subunit complex, the constitutive centromere associated network (CCAN), connects between the specialized centromeric chromatin, marked by the histone H3 variant CENP-A, and the spindle-binding moiety of the kinetochore. Here, we report a cryo-electron microscopy structure of human CCAN. We highlight unique features such as the pseudo GTPase CENP-M and report how a crucial CENP-C motif binds the CENP-LN complex. The CCAN structure has implications for the mechanism of specific recognition of the CENP-A nucleosome. A model consistent with our structure depicts the CENP-C-bound nucleosome as connected to the CCAN through extended, flexible regions of CENP-C. An alternative model identifies both CENP-C and CENP-N as specificity determinants but requires CENP-N to bind CENP-A in a mode distinct from the classical nucleosome octamer. A cryo-EM structure of the CCAN is reported The structure rationalizes relative positions and roles of the 16 CCAN subunits The CCAN core is shown to prefer naked DNA to CENP-A nucleosomes Several possible models of organization of centromeric chromatin are discussed The centromere is a specialized chromosome locus that seeds the kinetochore, a macromolecular complex that promotes chromosome segregation. Pesenti, Raisch et al. report the structure of the constitutive centromere-associated network (CCAN), a multi-subunit assembly that surrounds CENP-A/CenH3, the centromere’s epigenetic marker. The structure raises fundamental new questions on centromere organization.
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影响因子：
16
作者：
Camahort, Raymond;Shivaraju, Manjunatha;Mattingly, Mark;Li, Bing;Nakanishi, Shima;Zhu, Dongxiao;Shilatifard, Ali;Workman, Jerry L.;Gerton, Jennifer L.
通讯作者：
Gerton, Jennifer L.
影响因子：
21.3
作者：
Carroll, Christopher W.;Silva, Mariana C. C.;Godek, Kristina M.;Jansen, Lars E. T.;Straight, Aaron F.
通讯作者：
Straight, Aaron F.
DOI：
10.1083/jcb.201001013
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carroll CW;Milks KJ;Straight AF
通讯作者：
Straight AF
影响因子：
7.7
作者：
Ali-Ahmad, Ahmad;Bilokapic, Silvija;Sekulic, Nikolina
通讯作者：
Sekulic, Nikolina
影响因子：
9.2
作者：
Allu, Praveen Kumar;Dawicki-McKenna, Jennine M.;Black, Ben E.
通讯作者：
Black, Ben E.