A single amino acid change in protein synthesis initiation factor 4G renders cap-dependent translation resistant to picornaviral 2A proteases

Biochemistry
B J Lamphear, R E Rhoads

Abstract

Infection of cells with picornaviruses of the rhino-, aphtho-, and enterovirus groups causes a shut-off in cap-dependent translation of cellular mRNAs but permits cap-independent viral RNA translation to proceed. This shut-off is thought to be mediated in part by the proteolytic cleavage of eukaryotic initiation factor 4G (eIF4G), although there is evidence to the contrary. Cleavage of eIF4G results in the separation of the eIF4E-binding domain from the ribosome- and helicase-binding domains of the factor, thereby limiting the ability of eIF4G to function in cap-dependent recruitment of mRNAs. Previously we determined the cleavage site within eIF4G targeted by the 2A proteases from human coxsackievirus serotype B4 and human rhinovirus serotype 2 using highly purified eIF4F and recombinant proteases. To examine further the role proteolysis of eIF4G plays in shut-off of translation, we altered the 2A cleavage site in human eIF4G by site-directed mutagenesis. Strikingly, the replacement of one amino acid at the 2A cleavage site resulted in a protein that is approximately 100-fold resistant to cleavage by coxsackievirus 2A protease and 10-50-fold for rhinovirus 2A. Alteration of the cleavage site had no effect on factor activity si...Continue Reading

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Citations

May 3, 2007·Genes & Development·Laura L Almstead, Peter Sarnow
May 22, 2004·European Journal of Biochemistry·Bhavesh JoshiRosemary Jagus
May 5, 2006·Applied and Environmental Microbiology·Yu-Chen HwangMarylynn V Yates
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Oct 7, 2000·The Journal of Biological Chemistry·N L KorneevaR E Rhoads
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Aug 10, 2019·Frontiers in Cellular and Infection Microbiology·Paul J HansonDecheng Yang
Apr 1, 2000·The Journal of Biological Chemistry·B D KeiperR E Rhoads

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