title: The crystal structure of the N-terminal region of BUB1 provides insight into the mechanism of BUB1 recruitment to kinetochores.
abstract: 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 angstroms 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.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK. victor@cryst.bioc.cam.ac.uk
authors.forename: Victor M
authors.initials: VM
authors.lastname: Bolanos-Garcia
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kiyomitsu
authors.forename: Sheena
authors.initials: S
authors.lastname: D'Arcy
authors.forename: Dimitri Y
authors.initials: DY
authors.lastname: Chirgadze
authors.forename: J Günter
authors.initials: JG
authors.lastname: Grossmann
authors.forename: Dijana
authors.initials: D
authors.lastname: Matak-Vinkovic
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Venkitaraman
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yanagida
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D018386:Kinetochores / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases