Structure of Protein Phosphatase 2A Core Enzyme Bound to Tumor-Inducing Toxins

Yongna Xing; Yanhui Xu; Yu Chen; Philip D Jeffrey; Yang Chao; Zheng Lin; Zhu Li; Stefan Strack; Jeffry B Stock; Yigong Shi

doi:10.1016/j.cell.2006.09.025

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Structure of Protein Phosphatase 2A Core Enzyme Bound to Tumor-Inducing Toxins

Journal article

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Structure of Protein Phosphatase 2A Core Enzyme Bound to Tumor-Inducing Toxins

Yongna Xing, Yanhui Xu, Yu Chen, Philip D Jeffrey, Yang Chao, Zheng Lin, Zhu Li, Stefan Strack, Jeffry B Stock and Yigong Shi

Cell (Cambridge), Vol.127(2), pp.341-353

10/20/2006

DOI: 10.1016/j.cell.2006.09.025

PMID: 17055435

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Abstract

The serine/threonine phosphatase protein phosphatase 2A (PP2A) plays an essential role in many aspects of cellular functions and has been shown to be an important tumor suppressor. The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a 36 kDa catalytic subunit. Here we report the crystal structures of the PP2A core enzyme bound to two of its inhibitors, the tumor-inducing agents okadaic acid and microcystin-LR, at 2.6 and 2.8 Å resolution, respectively. The catalytic subunit recognizes one end of the elongated scaffolding subunit by interacting with the conserved ridges of HEAT repeats 11–15. Formation of the core enzyme forces the scaffolding subunit to undergo pronounced structural rearrangement. The scaffolding subunit exhibits considerable conformational flexibility, which is proposed to play an essential role in PP2A function. These structures, together with biochemical analyses, reveal significant insights into PP2A function and serve as a framework for deciphering the diverse roles of PP2A in cellular physiology.

Details

Title: Subtitle: Structure of Protein Phosphatase 2A Core Enzyme Bound to Tumor-Inducing Toxins
Creators: Yongna Xing - Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
Yanhui Xu - Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
Yu Chen - Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
Philip D Jeffrey - Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
Yang Chao - Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
Zheng Lin - Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
Zhu Li - Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
Stefan Strack - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Jeffry B Stock - Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
Yigong Shi - Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.127(2), pp.341-353
Publisher: Elsevier Inc
DOI: 10.1016/j.cell.2006.09.025
PMID: 17055435
ISSN: 0092-8674
eISSN: 1097-4172
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health
Language: English
Date published: 10/20/2006
Academic Unit: Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984040475302771

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