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Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins

Yongna Xing1, Yanhui Xu, Yu Chen

  • 1Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, NJ 08544, USA.

Cell
|October 24, 2006
PubMed

Insights

Structural insights into protein phosphatase 2A (PP2A) reveal how inhibitors bind to this tumor suppressor enzyme. Understanding PP2A

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Oncology

Background:

  • Protein phosphatase 2A (PP2A) is a crucial serine/threonine phosphatase involved in numerous cellular processes.
  • PP2A functions as a significant tumor suppressor, highlighting its importance in cancer biology.
  • The PP2A core enzyme consists of a scaffolding subunit (65 kDa) and a catalytic subunit (36 kDa).

Purpose of the Study:

  • To elucidate the structural basis of PP2A inhibition by okadaic acid and microcystin-LR.
  • To understand the interaction between the PP2A core enzyme subunits.
  • To provide a structural framework for comprehending PP2A's diverse cellular roles.

Main Methods:

  • X-ray crystallography was employed to determine the structures of the PP2A core enzyme bound to inhibitors.
  • High-resolution structures were obtained at 2.6 Å (okadaic acid) and 2.8 Å (microcystin-LR).
  • Biochemical analyses were integrated with structural data.

Main Results:

  • The crystal structures of the PP2A core enzyme with okadaic acid and microcystin-LR were determined.
  • The catalytic subunit interacts with HEAT repeats 11-15 of the scaffolding subunit.
  • Core enzyme formation induces significant structural rearrangements in the scaffolding subunit, revealing its conformational flexibility.

Conclusions:

  • The determined structures offer critical insights into PP2A function and inhibition mechanisms.
  • The conformational flexibility of the scaffolding subunit is proposed to be vital for PP2A activity.
  • These findings provide a foundation for further research into PP2A's roles in cellular physiology and disease.

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