Targeting the lateral interactions of transmembrane domain 5 of Epstein-Barr virus latent membrane protein 1.

Academic Article

Abstract

  • The lateral transmembrane protein-protein interaction has been regarded as "undruggable" despite its importance in many biological processes. The homo-trimerization of transmembrane domain 5 (TMD-5) of latent membrane protein 1 (LMP-1) is critical for the constitutive oncogenic activation of the Epstein-Barr virus (EBV). Herein, we report a small molecule agent, NSC 259242 (compound 1), to be a TMD-5 self-association disruptor. Both the positively charged acetimidamide functional groups and the stilbene backbone of compound 1 are essential for its inhibitory activity. Furthermore, cell-based assays revealed that compound 1 inhibits full-length LMP-1 signaling in EBV infected B cells. These studies demonstrated a new strategy for identifying small molecule disruptors for investigating transmembrane protein-protein interactions.

    • Authors

  • Wang, Xiaohui
  • Saludes, Jonel P
  • Zhao, Tina X
  • Csakai, Adam
  • Fiorini, Zeno
  • Chavez, Sherry A
  • Li, Jing
  • Lee, Gui-in
  • Varga, Krisztina
  • Yin, Hang

    • Status

    Publication Date

  • September 2012

    • Has Subject Area

    Published In

  • BBA: Biomembranes  Journal

    • Keywords

  • Antiviral Agents
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Herpesvirus 4, Human
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Biological
  • Models, Chemical
  • Models, Molecular
  • Models, Statistical
  • Molecular Conformation
  • NF-kappa B
  • Nitric Oxide
  • Peptides
  • Protein Binding
  • Protein Structure, Tertiary
  • Signal Transduction
  • Spectrometry, Fluorescence
  • Stilbamidines
  • Viral Matrix Proteins

    • Digital Object Identifier (doi)

    Start Page

  • 2282

    • End Page

  • 2289

    • Volume

  • 1818

    • Issue

  • 9