The Crystal Structure of the N-Terminal Region of BUB1 Provides Insight into the Mechanism of BUB1 Recruitment to Kinetochores

被引：49

作者：

Bolanos-Garcia, Victor M. ^{[1
]}

Kiyomitsu, Tomomi ^{[2
]}

D'Arcy, Sheena ^{[1
]}

Chirgadze, Dimitri Y. ^{[1
]}

Grossmann, J. Guenter ^{[3
]}

Matak-Vinkovic, Dijana ^{[4
]}

Venkitaraman, Ashok R. ^{[5
]}

Yanagida, Mitsuhiro ^{[2
]}

Robinson, Carol V. ^{[4
]}

Blundell, Tom L. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England

[2] Kyoto Univ, Grad Sch Biostudies, CREST Res Program JST, Kyoto 6068501, Japan

[3] Univ Liverpool, Sch Biol Sci, Mol Biophys Grp, Liverpool L69 7ZB, Merseyside, England

[4] Univ Cambridge, Dept Chem, Cambridge CB2 1GA, England

[5] Hutchison MRC Res Ctr, Cambridge CB2 0XZ, England

来源：

STRUCTURE | 2009年 / 17卷 / 01期

基金：

英国惠康基金;

关键词：

SPINDLE CHECKPOINT FUNCTION; MITOTIC CHECKPOINT; CHROMOSOME; DOMAIN; GENE; LOCALIZATION; MUTATIONS; SHUGOSHIN; PROTEINS; SEQUENCE;

D O I：

10.1016/j.str.2008.10.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 angstrom 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.

引用

页码：105 / 116

页数：12

共 48 条

[1]

BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice [J].