Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N

被引:88
作者
Chittori, Sagar [1 ]
Hong, Jingjun [2 ]
Saunders, Hayden [2 ]
Feng, Hanqiao [2 ]
Ghirlando, Rodolfo [3 ]
Kelly, Alexander E. [2 ]
Bai, Yawen [2 ]
Subramaniam, Sriram [1 ]
机构
[1] NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA
[2] NCI, Lab Biochem & Mol Biol, CCR, NIH, Bethesda, MD 20892 USA
[3] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA
关键词
A NUCLEOSOMES; CHROMATIN; HISTONE; ORGANIZATION; ARCHITECTURE; HETERODIMER; COMPLEX;
D O I
10.1126/science.aar2781
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Accurate chromosome segregation requires the proper assembly of kinetochore proteins. A key step in this process is the recognition of the histone H3 variant CENP-A in the centromeric nucleosome by the kinetochore protein CENP-N. We report cryo-electron microscopy (cryo-EM), biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N. We show that human CENP-N confers binding specificity through interactions with the L1 loop of CENP-A, stabilized by electrostatic interactions with the nucleosomal DNA. Mutational analyses demonstrate analogous interactions in Xenopus, which are further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with the coevolution of CENP-N and CENP-A and establish the structural basis for recognition of the CENP-A nucleosome to enable kinetochore assembly and centromeric chromatin organization.
引用
收藏
页码:339 / +
页数:5
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