Please use this identifier to cite or link to this item: https://doi.org/10.1007/s13238-016-0283-4
Title: Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization
Authors: Wang, J
Wang, Z
Yu, T
Yang, H
Virshup, D.M 
Kops, G.J.P.L
Lee, S.H 
Zhou, W
Li, X
Xu, W
Rao, Z
Keywords: binding protein
Bub1 related protein
phosphopeptide
phosphoprotein phosphatase 2A
BUB1 protein, human
cell cycle protein
multienzyme complex
phosphoprotein phosphatase 2
PP2A-B56alpha protein, human
protein serine threonine kinase
SGOL1 protein, human
Article
cell division
chemical mutagenesis
chromosome segregation
crystal structure
DNA binding motif
enzyme specificity
gene expression regulation
human
isothermal titration calorimetry
kinetochore microtubule
M phase cell cycle checkpoint
polyacrylamide gel electrophoresis
priority journal
protein expression
protein interaction
protein localization
protein phosphorylation
protein processing
protein purification
proteomics
transcription regulation
binding site
chemistry
protein motif
protein quaternary structure
X ray crystallography
Amino Acid Motifs
Binding Sites
Cell Cycle Proteins
Crystallography, X-Ray
Humans
Multienzyme Complexes
Protein Phosphatase 2
Protein Structure, Quaternary
Protein-Serine-Threonine Kinases
Issue Date: 2016
Citation: Wang, J, Wang, Z, Yu, T, Yang, H, Virshup, D.M, Kops, G.J.P.L, Lee, S.H, Zhou, W, Li, X, Xu, W, Rao, Z (2016). Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization. Protein and Cell 7 (7) : 516-526. ScholarBank@NUS Repository. https://doi.org/10.1007/s13238-016-0283-4
Rights: Attribution 4.0 International
Abstract: ABSTRACT: Protein phosphatase 2A (PP2A) accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a catalytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kinetochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interaction plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attachment. Here we present the crystal structure of a PP2A B56-BubR1 complex, which demonstrates that a conserved BubR1 LxxIxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxIxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets. © 2016, The Author(s).
Source Title: Protein and Cell
URI: https://scholarbank.nus.edu.sg/handle/10635/179923
ISSN: 1674800X
DOI: 10.1007/s13238-016-0283-4
Rights: Attribution 4.0 International
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