ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail

被引：43

作者：

Bertran, M. Teresa ^{[1
]}

Mouilleron, Stephane ^{[2
]}

Zhou, Yanxiang ^{[1
]}

Bajaj, Rakhi ^{[3
]}

Uliana, Federico ^{[4
]}

Kumar, Ganesan Senthil ^{[3
]}

van Drogen, Audrey ^{[4
]}

Lee, Rebecca ^{[2
]}

Banerjee, Jennifer J. ^{[1
]}

Hauri, Simon ^{[4
]}

O'Reilly, Nicola ^{[5
]}

Gstaiger, Matthias ^{[4
]}

Page, Rebecca ^{[3
]}

Peti, Wolfgang ^{[3
]}

Tapon, Nicolas ^{[1
]}

机构：

[1] Francis Crick Inst, Apoptosis & Proliferat Control Lab, 1 Midland Rd, London NW1 1AT, England

[2] Francis Crick Inst, Struct Biol Sci Technol Platform, 1 Midland Rd, London NW1 1AT, England

[3] Univ Arizona, Dept Chem & Biochem, 1041 E Lowell St,Biosci West 517, Tucson, AZ 85721 USA

[4] Swiss Fed Inst Technol, Dept Biol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland

[5] Francis Crick Inst, Peptide Chem Lab, 1 Midland Rd, London NW1 1AT, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

欧盟第七框架计划; 英国医学研究理事会; 英国惠康基金;

关键词：

STRUCTURAL BASIS; PHOSPHATASE; SUBCELLULAR LOCALIZATIONS; BINDING; SPECIFICITY; RECOGNITION; SUBSTRATE; INTERACTS; PROTEOME; ISOFORMS;

D O I：

10.1038/s41467-019-08686-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Serine/threonine phosphatases such as PP1 lack substrate specificity and associate with a large array of targeting subunits to achieve the requisite selectivity. The tumour suppressor ASPP (apoptosis-stimulating protein of p53) proteins associate with PP1 catalytic subunits and are implicated in multiple functions from transcriptional regulation to cell junction remodelling. Here we show that Drosophila ASPP is part of a multiprotein PP1 complex and that PP1 association is necessary for several in vivo functions of Drosophila ASPP. We solve the crystal structure of the human ASPP2/PP1 complex and show that ASPP2 recruits PP1 using both its canonical RVxF motif, which binds the PP1 catalytic domain, and its SH3 domain, which engages the PP1 C-terminal tail. The ASPP2 SH3 domain can discriminate between PP1 isoforms using an acidic specificity pocket in the n-Src domain, providing an exquisite mechanism where multiple motifs are used combinatorially to tune binding affinity to PP1.

引用

页数：19

共 77 条

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