2022 AMI Online Salon

The Structural Basis of PTEN Regulation by Multi-Site Phosphorylation

Project Details

  • Entrant Name:  Jennifer Wang
  • Client: Sandra Gabelli, Fabian de Kok-Mercado, Lydia Gregg
  • Copyright:  Jennifer A. Wang, 2021
  • Medium/software used: Cinema 4D, Pymol, ePMV, Adobe Photoshop
  • Final presentation format: Digital Poster
  • Primary Audience: Structural biologists, oncologists

Project Description

This figure illustrates the structural differences between PTEN in its active and inactive states in a cellular landscape. PTEN is a phosphatidylinositol-3,4,5-triphosphate (PIP3) phospholipid phosphatase that typically dephosphorylates PIP3 into PIP2. However, it is often silenced or mutated in cancer cells. PTEN structure consists of a catalytic domain, C2 domain, and C-terminal tail. When catalytically active, the C2 domain associates with the cell membrane and the C-terminal tail remains open for PIP3 to enter the active site. An inset shows the helix structure of PTEN’s catalytic domain, where the position of the residues creates a positively charged surface. Once the C-terminal tail becomes phosphorylated at four key sites (S380, T382, T383, and S385), the tail closes on the active site and PTEN disassociates from the cell membrane. An N-terminal a-helix is crucial for PTEN catalysis but is disordered upon C-terminal tail interaction or when PTEN is in a closed state.