A Conserved Motif Provides Binding Specificity to the PP2A-B56 Phosphatase

被引：206

作者：

Hertz, Emil Peter Thrane ^{[1
]}

Kruse, Thomas ^{[1
]}

Davey, Norman E. ^{[2
]}

Lopez-Mendez, Blanca ^{[1
]}

Sigurdsson, Jon Otti ^{[1
]}

Montoya, Guillermo ^{[1
]}

Olsen, Jesper V. ^{[1
]}

Nilsson, Jakob ^{[1
]}

机构：

[1] Univ Copenhagen, Fac Hlth & Med Sci, Ctr Prot Res, Novo Nordisk Fdn, DK-2200 Copenhagen, Denmark

[2] Univ Coll Dublin, Conway Inst Biomol & Biomed Sci, Dublin 4, Ireland

来源：

MOLECULAR CELL | 2016年 / 63卷 / 04期

关键词：

AURORA-B; FAMILY; BUBR1; 2A; RECRUITMENT; KINASE;

D O I：

10.1016/j.molcel.2016.06.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Dynamic protein phosphorylation is a fundamental mechanism regulating biological processes in all organisms. Protein phosphatase 2A (PP2A) is the main source of phosphatase activity in the cell, but the molecular details of substrate recognition are unknown. Here, we report that a conserved surface-exposed pocket on PP2A regulatory B56 subunits binds to a consensus sequence on interacting proteins, which we term the LxxIxE motif. The composition of the motif modulates the affinity for B56, which in turn determines the phosphorylation status of associated substrates. Phosphorylation of amino acid residues within the motif increases B56 binding, allowing integration of kinase and phosphatase activity. We identify conserved LxxIxE motifs in essential proteins throughout the eukaryotic domain of life and in human viruses, suggesting that the motifs are required for basic cellular function. Our study provides a molecular description of PP2A binding specificity with broad implications for understanding signaling in eukaryotes.

引用

页码：686 / 695

页数：10

共 27 条

[1] Liprinα1 interacts with PP2A B56γ [J].