1. Targeting the lateral interactions of transmembrane domain 5 of Epstein-Barr virus latent membrane protein 1
- Author
-
Tina X. Zhao, Hang Yin, Sherry A. Chavez, Adam Csakai, Zeno Fiorini, Gui-in Lee, Jonel P. Saludes, Jing Li, Xiaohui Wang, and Krisztina Varga
- Subjects
Models, Molecular ,Herpesvirus 4, Human ,Magnetic Resonance Spectroscopy ,Stilbamidines ,Biophysics ,Molecular Conformation ,010402 general chemistry ,Nitric Oxide ,01 natural sciences ,Biochemistry ,Antiviral Agents ,Models, Biological ,Article ,Protein–protein interaction ,Transmembrane domain ,Epstein–Barr virus ,Viral Matrix Proteins ,03 medical and health sciences ,Protein structure ,Latent membrane protein 1 ,Cell Line, Tumor ,Humans ,030304 developmental biology ,0303 health sciences ,Viral matrix protein ,Models, Statistical ,Dose-Response Relationship, Drug ,Chemistry ,NF-kappa B ,Cell Biology ,Epstein–Barr virus latent membrane protein 1 ,Small molecule ,Transmembrane protein ,0104 chemical sciences ,Cell biology ,Protein Structure, Tertiary ,High throughput screen ,Spectrometry, Fluorescence ,Models, Chemical ,Small molecule inhibitor ,Signal transduction ,Peptides ,Protein Binding ,Signal Transduction - 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.
- Published
- 2012