A viral protein that blocks Arf1-mediated COP-I assembly by inhibiting the guanine nucleotide exchange factor GBF1.
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.
Wessels
Els
E
Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Duijsings
Daniël
D
Niu
Ting-Kuang
TK
Neumann
Steffi
S
Oorschot
Viola M
VM
de Lange
Frank
F
Lanke
Kjerstin H W
KH
Klumperman
Judith
J
Henke
Andreas
A
Jackson
Catherine L
CL
Melchers
Willem J G
WJ
van Kuppeveld
Frank J M
FJ
D020823:ADP-Ribosylation Factor 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D020755:Coat Protein Complex I / Q000187:drug effects / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D006056:Golgi Apparatus / Q000187:drug effects / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D023421:Models, Animal; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D014764:Viral Proteins / Q000494:pharmacology*
C500427:3A protein, coxsackievirus B; D020755:Coat Protein Complex I; D020662:Guanine Nucleotide Exchange Factors; D014764:Viral Proteins; D020823:ADP-Ribosylation Factor 1