The crystal structure of the N-terminal region of BUB1 provides insight into the mechanism of BUB1 recruitment to kinetochores.
The crystal structure of the N-terminal region of BUB1 provides insight into the mechanism of BUB1 recruitment to kinetochores.
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DOI：
10.1016/j.str.2008.10.015
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发表时间：
2009-01-14
期刊：
影响因子：
--
通讯作者：
Blundell TL
中科院分区：
文献类型：
--
作者：
Bolanos-Garcia VM;Kiyomitsu T;D'Arcy S;Chirgadze DY;Grossmann JG;Matak-Vinkovic D;Venkitaraman AR;Yanagida M;Robinson CV;Blundell TL
中心有丝分裂检查点成分BUB1与有丝分裂着丝点蛋白Blinkin的相互作用是着丝点定位和BUB1在有丝分裂纺锤体组装检查点中的功能所必需的，这是细胞周期的调节机制，确保了染色体在从中期到后期过渡期间的均匀分布。本文报道了BUB1 n端区1.74 Å分辨率的晶体结构。该结构被组织为四肽基序的三个不同单元的串联排列。体内天然突变体和位点特异性突变体的功能分析鉴定了与Blinkin相互作用重要的人BUB1残基，并确定了一个潜在的治疗兴趣区域。该结构提供了对BUB1对blinkin特异性识别的分子基础的深入了解，并从更广泛的角度了解了在检查点激活的细胞中介导BUB1着丝点定位的机制。
The interaction of the central mitotic checkpoint component BUB1 with the mitotic kinetochore protein Blinkin is required for the kinetochore localization and function of BUB1 in the mitotic spindle assembly checkpoint, the regulatory mechanism of the cell cycle that ensures the even distribution of chromosomes during the transition from metaphase to anaphase. Here, we report the 1.74 Å resolution crystal structure of the N-terminal region of BUB1. The structure is organized as a tandem arrangement of three divergent units of the tetratricopeptide motif. Functional assays in vivo of native and site-specific mutants identify the residues of human BUB1 important for the interaction with Blinkin and define one region of potential therapeutic interest. The structure provides insight into the molecular basis of Blinkin-specific recognition by BUB1 and, on a broader perspective, of the mechanism that mediates kinetochore localization of BUB1 in checkpoint-activated cells.
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