A Viral Protein That Blocks Arf1-mediated COP-I Assembly by Inhibiting the Guanine Nucleotide Exchange Factor GBF1

Dev Cell. 2006 Aug;11(2):191-201. doi: 10.1016/j.devcel.2006.06.005.

Abstract

Many viruses modify cellular processes for their own benefit. The enterovirus 3A protein inhibits endoplasmic reticulum (ER)-to-Golgi transport, a function previously suggested to be important for viral suppression of immune responses. Here, we show that a virus carrying a 3A protein defective in inhibiting ER-to-Golgi transport is indeed less virulent in mice, and we unravel the mechanism by which 3A inhibits this trafficking step. Evidence is provided that 3A inhibits the activation of the GTPase ADP-ribosylation factor 1 (Arf1), which regulates the recruitment of the COP-I coat complex to membranes. 3A specifically inhibits the function of GBF1, a guanine nucleotide exchange factor for Arf1, by interacting with its N terminus. By specifically interfering with GBF1-mediated Arf1 activation, 3A may prove a valuable tool in dissecting the early steps of the secretory pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 1 / antagonists & inhibitors*
  • ADP-Ribosylation Factor 1 / metabolism
  • Animals
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / physiology
  • Cell Membrane / ultrastructure
  • Chlorocebus aethiops
  • Coat Protein Complex I / drug effects
  • Coat Protein Complex I / metabolism*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / physiology
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / physiology
  • Guanine Nucleotide Exchange Factors / antagonists & inhibitors*
  • Guanine Nucleotide Exchange Factors / biosynthesis
  • Guanine Nucleotide Exchange Factors / physiology
  • Mice
  • Models, Animal
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Viral Proteins / pharmacology*

Substances

  • 3A protein, coxsackievirus B
  • Coat Protein Complex I
  • Guanine Nucleotide Exchange Factors
  • Viral Proteins
  • ADP-Ribosylation Factor 1