Structural analysis of fungal CENP-H/I/K homologs reveals a conserved assembly mechanism underlying proper chromosome alignment
Hu, Liqiao1; Huang, Hao1; Hei, Mohan1; Yang, Yang2; Li, Sheng3; Liu, Yunshan1; Dou, Zhen4; Wu, Mengying1; Li, Jie5; Wang, Guang-zhong5
2019-01-10
发表期刊NUCLEIC ACIDS RESEARCH
ISSN0305-1048
卷号47期号:1页码:468-479
发表状态已发表
DOI10.1093/nar/gky1108
摘要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.
收录类别SCI ; SCIE
语种英语
资助项目Natural Science Foundation of Hubei Province of China[2015CFB484] ; Natural Science Foundation of Hubei Province of China[2015CFB689]
WOS研究方向Biochemistry & Molecular Biology
WOS类目Biochemistry & Molecular Biology
WOS记录号WOS:000462586700040
出版者OXFORD UNIV PRESS
WOS关键词CENTROMERIC NUCLEOSOME RECOGNITION ; OUTER KINETOCHORE ; A NUCLEOSOMES ; MOLECULAR-BASIS ; COMPLEX ; CHROMATIN ; RECRUITMENT ; COMPONENTS ; PLATFORM ; FORMS
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/34253
专题免疫化学研究所_特聘教授组_结构生物化学实验室
通讯作者He, Xiaojing; Tian, Wei
作者单位1.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Minist Educ, Key Lab Mol Biophys, Wuhan 430074, Hubei, Peoples R China
2.Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA
3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
4.Univ Sci & Technol China, Hefei Natl Res Ctr Phys Sci Microscale, Anhui Key Lab Cellular Dynam & Chem Biol, Hefei 230027, Anhui, Peoples R China
5.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci,CAS MPG Partner Inst Compu, Shanghai Inst Nutr & Hlth,CAS Key Lab Computat Bi, Shanghai 200031, Peoples R China
6.Tulane Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA
7.Huazhong Univ Sci & Technol, Inst Brain Res, Collaborat Innovat Ctr Brain Sci, Wuhan 430030, Hubei, Peoples R China
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Hu, Liqiao,Huang, Hao,Hei, Mohan,et al. Structural analysis of fungal CENP-H/I/K homologs reveals a conserved assembly mechanism underlying proper chromosome alignment[J]. NUCLEIC ACIDS RESEARCH,2019,47(1):468-479.
APA Hu, Liqiao.,Huang, Hao.,Hei, Mohan.,Yang, Yang.,Li, Sheng.,...&Tian, Wei.(2019).Structural analysis of fungal CENP-H/I/K homologs reveals a conserved assembly mechanism underlying proper chromosome alignment.NUCLEIC ACIDS RESEARCH,47(1),468-479.
MLA Hu, Liqiao,et al."Structural analysis of fungal CENP-H/I/K homologs reveals a conserved assembly mechanism underlying proper chromosome alignment".NUCLEIC ACIDS RESEARCH 47.1(2019):468-479.
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