Structural analysis of fungal CENP-H/I/K homologs reveals a conserved assembly mechanism underlying proper chromosome alignment.
Structural analysis of fungal CENP-H/I/K homologs reveals a conserved assembly mechanism underlying proper chromosome alignment.
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真菌 CENP-H/I/K 同源物的结构分析揭示了正确染色体排列背后的保守组装机制。
DOI：
10.1093/nar/gky1108
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发表时间：
2019-01-10
影响因子：
14.9
通讯作者：
Tian W
中科院分区：
文献类型：
--
作者：
Hu L;Huang H;Hei M;Yang Y;Li S;Liu Y;Dou Z;Wu M;Li J;Wang GZ;Yao X;Liu H;He X;Tian W
着丝粒是一种蛋白质复合物，对于染色体的正确分离至关重要。作为内着丝粒的核心成员，CENP-H/I/K复合体中各亚基的缺陷会导致着丝粒功能障碍，从而导致染色体错误分离和细胞死亡。然而，人们对 CENP-H/I/K 复合物如何组装和促进着丝粒功能知之甚少。我们在此确定了来自嗜热毛壳菌的 CENP-I N-末端的晶体结构及其与来自土生梭孢壳的 CENP-H/K 的复合物，并验证了所识别的相互作用。结构和生化分析表明CENP-H和CENP-K通过N端和C端相互作用形成异二聚体。 CENP-I通过与CENP-H的C端结合而整合到CENP-H/K复合物中，导致形成CENP-H夹在CENP-K和CENP-I之间的三元复合物。我们的序列比较和突变分析表明，CENP-H/I/K 复合物的这种结构在人类中是保守的。突变 CENP-H 与 CENP-K 或 CENP-I 的结合界面显着减少了它们在着丝粒的定位，并在有丝分裂过程中诱导大量染色体排列缺陷，这表明所确定的相互作用对于着丝粒和着丝粒功能的 CENP-H/I/K 复合物组装至关重要。总而言之，我们的研究结果揭示了 CENP-H/I/K 复合物在进化上保守的组装机制，这对于正确的染色体排列至关重要。
The kinetochore is a proteinaceous complex that is essential for proper chromosome segregation. As a core member of the inner kinetochore, defects of each subunit in the CENP-H/I/K complex cause dysfunction of kinetochore that leads to chromosome mis-segregation and cell death. However, how the CENP-H/I/K complex assembles and promotes kinetochore function are poorly understood. We here determined the crystal structures of CENP-I N-terminus alone from Chaetomium thermophilum and its complex with CENP-H/K from Thielavia terrestris, and verified the identified interactions. The structures and biochemical analyses show that CENP-H and CENP-K form a heterodimer through both N- and C-terminal interactions. CENP-I integrates into the CENP-H/K complex by binding to the C-terminus of CENP-H, leading to formation of the ternary complex in which CENP-H is sandwiched between CENP-K and CENP-I. Our sequence comparisons and mutational analyses showed that this architecture of the CENP–H/I/K complex is conserved in human. Mutating the binding interfaces of CENP-H for either CENP-K or CENP-I significantly reduced their localizations at centromeres and induced massive chromosome alignment defects during mitosis, suggesting that the identified interactions are critical for CENP-H/I/K complex assembly at the centromere and kinetochore function. Altogether, our findings unveil the evolutionarily conserved assembly mechanism of the CENP-H/I/K complex that is critical for proper chromosome alignment.
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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：
10.1126/science.1259308
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Falk SJ;Guo LY;Sekulic N;Smoak EM;Mani T;Logsdon GA;Gupta K;Jansen LE;Van Duyne GD;Vinogradov SA;Lampson MA;Black BE
通讯作者：
Black BE
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：
64.5
作者：
Hori, Tetsuya;Amano, Miho;Fukagawa, Tatsuo
通讯作者：
Fukagawa, Tatsuo
伪GTPASE CENP-M驱动人类动物组件。
影响因子：
7.7
作者：
Basilico F;Maffini S;Weir JR;Prumbaum D;Rojas AM;Zimniak T;De Antoni A;Jeganathan S;Voss B;van Gerwen S;Krenn V;Massimiliano L;Valencia A;Vetter IR;Herzog F;Raunser S;Pasqualato S;Musacchio A
通讯作者：
Musacchio A