Chemical and structural approaches to investigate PTEN function and regulation

Thibault Viennet, Santiago Rodriguez Ospina, Yunqi Lu, Anna Cui, Haribabu Arthanari, Daniel R. Dempsey*

*Corresponding author for this work

Research output: Contribution to book/anthology/report/proceedingBook chapterResearchpeer-review

7 Citations (Scopus)

Abstract

Phosphatase and tensin homolog is a lipid phosphatase that serves as the major negative regulator of the PI3K/AKT pathway. It catalyzes the 3′-specific dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to generate PIP2. PTEN's lipid phosphatase function depends on several domains, including an N-terminal segment spanning the first 24 amino acids, which results in a catalytically impaired enzyme when mutated. Furthermore, PTEN is regulated by a cluster of phosphorylation sites located on its C-terminal tail at Ser380, Thr382, Thr383, and Ser385, which drives its conformation from an open to a closed autoinhibited but stable state. Herein, we discuss the protein chemical strategies we used to reveal the structure and mechanism of how PTEN's terminal regions govern its function.

Original languageEnglish
Title of host publicationIntegrated Methods in Protein Biochemistry : Part C
EditorsArun K. Shukla
Number of pages30
Volume682
PublisherELSEVIER ACADEMIC PRESS INC
Publication dateJan 2023
Pages289-318
ISBN (Print)9780443185922
DOIs
Publication statusPublished - Jan 2023
Externally publishedYes
SeriesMethods in Enzymology
Volume682
ISSN0076-6879

Keywords

  • Biomolecular NMR
  • C-terminal tail
  • Expressed protein ligation
  • Phosphorylation
  • Protein X-ray crystallography
  • PTEN
  • PTEN Phosphohydrolase/genetics
  • Phosphatidylinositol 3-Kinases/metabolism
  • Lipids
  • Amino Acids/metabolism

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