Structure of a Blinkin-BUBR1 complex reveals an interaction crucial for kinetochore-mitotic checkpoint regulation via an unanticipated binding Site.
Structure of a Blinkin-BUBR1 complex reveals an interaction crucial for kinetochore-mitotic checkpoint regulation via an unanticipated binding Site.
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DOI：
10.1016/j.str.2011.09.017
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发表时间：
2011-11-09
期刊：
影响因子：
5.7
通讯作者：
Blundell, Tom L.
中科院分区：
文献类型：
--
作者：
Bolanos-Garcia, Victor M.;Lischetti, Tiziana;Matak-Vinkovic, Dijana;Cota, Ernesto;Simpson, Pete J.;Chirgadze, Dimitri Y.;Spring, David R.;Robinson, Carol V.;Nilsson, Jakob;Blundell, Tom L.
基因组稳定性的维持依赖于纺锤体组装检查点（SAC），它通过延迟后期的开始，确保准确的染色体分离，直到所有染色体都正确地定向并附着在有丝分裂纺锤体上。BUB1和BUBR1激酶是这一过程的核心，通过与Blinkin相互作用，将SAC与着丝粒连接起来，着丝粒是连接微管和着丝粒DNA的大分子组装体。在这里，我们确定了与BUBR1相互作用至关重要的Blinkin基序，定义了相互作用的化学计量学和亲和力，并提出了2.2 Å分辨率的配合物晶体结构。该结构定义了一个意想不到的负责相互作用的BUBR1区域，并揭示了一个新的Blinkin基序，该基序在配体结合时经历了无序到有序的转变。我们还发现，一些参与结合Blinkin的BUBR1残基的替代导致SAC缺陷，从而提供了kinetochore-SAC信号传导识别机制的第一个分子细节。►BUBR1-Blinkin复合物的晶体结构定义了一个意想不到的BUBR1区域►一个新的Blinkin基序在BUBR1结合时经历了无序到有序的转变►结合Blinkin的BUBR1残基突变导致有丝分裂检查点受损
The maintenance of genomic stability relies on the spindle assembly checkpoint (SAC), which ensures accurate chromosome segregation by delaying the onset of anaphase until all chromosomes are properly bioriented and attached to the mitotic spindle. BUB1 and BUBR1 kinases are central for this process and by interacting with Blinkin, link the SAC with the kinetochore, the macromolecular assembly that connects microtubules with centromeric DNA. Here, we identify the Blinkin motif critical for interaction with BUBR1, define the stoichiometry and affinity of the interaction, and present a 2.2 Å resolution crystal structure of the complex. The structure defines an unanticipated BUBR1 region responsible for the interaction and reveals a novel Blinkin motif that undergoes a disorder-to-order transition upon ligand binding. We also show that substitution of several BUBR1 residues engaged in binding Blinkin leads to defects in the SAC, thus providing the first molecular details of the recognition mechanism underlying kinetochore-SAC signaling. ► Molecular details of the recognition mechanism underlying kinetochore-SAC signalling ► Crystal structure of a BUBR1-Blinkin complex defines an unanticipated BUBR1 region ► A novel Blinkin motif undergoes a disorder-to-order transition upon BUBR1 binding ► Mutation of BUBR1 residues that bind Blinkin lead to an impaired mitotic checkpoint
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影响因子：
11.8
作者：
Malureanu, Liviu A.;Jeganathan, Karthik B.;Hamada, Masakazu;Wasilewski, Lisa;Davenport, James;van Deursen, Jan M.
通讯作者：
van Deursen, Jan M.
影响因子：
21.3
作者：
Nilsson, Jakob;Yekezare, Mona;Minshull, Jeremy;Pines, Jonathon
通讯作者：
Pines, Jonathon
DOI：
10.1016/j.str.2008.10.015
发表时间：
2009-01-14
期刊：
Structure (London, England : 1993)
影响因子：
--
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
通讯作者：
Blundell TL
影响因子：
21.3
作者：
Lampson, MA;Kapoor, TM
通讯作者：
Kapoor, TM
影响因子：
11.4
作者：
Schittenhelm, Ralf B.;Chaleckis, Romanas;Lehner, Christian F.
通讯作者：
Lehner, Christian F.