Structure of a Blinkin-BUBR1 complex reveals an interaction crucial for kinetochore-mitotic checkpoint regulation via an unanticipated binding Site
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Structure of a Blinkin-BUBR1 complex reveals an interaction crucial for kinetochore-mitotic checkpoint regulation via an unanticipated binding Site. / Bolanos-Garcia, Victor M; Lischetti, Tiziana; Matak-Vinković, Dijana; Cota, Ernesto; Simpson, Pete J; Chirgadze, Dimitri Y; Spring, David R; Robinson, Carol V; Nilsson, Jakob; Blundell, Tom L.
In: Structure, Vol. 19, No. 11, 09.11.2011, p. 1691-700.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Structure of a Blinkin-BUBR1 complex reveals an interaction crucial for kinetochore-mitotic checkpoint regulation via an unanticipated binding Site
AU - Bolanos-Garcia, Victor M
AU - Lischetti, Tiziana
AU - Matak-Vinković, Dijana
AU - Cota, Ernesto
AU - Simpson, Pete J
AU - Chirgadze, Dimitri Y
AU - Spring, David R
AU - Robinson, Carol V
AU - Nilsson, Jakob
AU - Blundell, Tom L
N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.
PY - 2011/11/9
Y1 - 2011/11/9
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Binding Sites
KW - Cell Cycle Proteins
KW - Crystallography, X-Ray
KW - HeLa Cells
KW - Humans
KW - Kinetochores
KW - M Phase Cell Cycle Checkpoints
KW - Microtubule-Associated Proteins
KW - Mitosis
KW - Molecular Sequence Data
KW - Multiprotein Complexes
KW - Protein Binding
KW - Protein Interaction Domains and Motifs
KW - Protein-Serine-Threonine Kinases
KW - Two-Hybrid System Techniques
U2 - 10.1016/j.str.2011.09.017
DO - 10.1016/j.str.2011.09.017
M3 - Journal article
C2 - 22000412
VL - 19
SP - 1691
EP - 1700
JO - Structure
JF - Structure
SN - 0969-2126
IS - 11
ER -
ID: 46130850