Structural basis for competitive inhibition of eIF4G-Mnk1 interaction by the adenovirus 100-kilodalton protein

Journal of Virology
R CuestaR J Schneider

Abstract

Translation of most cellular mRNAs involves cap binding by the translation initiation complex. Among this complex of proteins are cap-binding protein eIF4E and the eIF4E kinase Mnk1. Cap-dependent mRNA translation generally correlates with Mnk1 phosphorylation of eIF4E when both are bound to eIF4G. During the late phase of adenovirus (Ad) infection translation of cellular mRNA is inhibited, which correlates with displacement of Mnk1 from eIF4G by the viral 100-kDa (100K) protein and dephosphorylation of eIF4E. Here we describe the molecular mechanism for 100K protein displacement of Mnk1 from eIF4G and elucidate a structural basis for eIF4G interaction with Mnk1 and 100K proteins and Ad inhibition of cellular protein synthesis. The eIF4G-binding site is located in an N-terminal 66-amino-acid peptide of 100K which is sufficient to bind eIF4G, displace Mnk1, block eIF4E phosphorylation, and inhibit eIF4F (cap)-dependent cellular mRNA translation. Ad 100K and Mnk1 proteins possess a common eIF4G-binding motif, but 100K protein binds more strongly to eIF4G than does Mnk1. Unlike Mnk1, for which binding to eIF4G is RNA dependent, competitive binding by 100K protein is RNA independent. These data support a model whereby 100K protein ...Continue Reading

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Citations

Jun 10, 2011·Cellular and Molecular Life Sciences : CMLS·Ewa Szolajska, Jadwiga Chroboczek
Jun 28, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Anna-Mary YoungIain A McNeish
Nov 22, 2005·Oncogene·Clodagh C O'Shea
Aug 18, 2004·Genes & Development·Qiaoran XiRobert J Schneider
Aug 10, 2007·Journal of Virology·Demetris C IacovidesFrank McCormick
Dec 16, 2011·Journal of Virology·Melanie SchmidThomas Dobner
May 5, 2010·Reviews in Medical Virology·Marcelo López-LastraFernando Valiente-Echeverría
Oct 26, 2005·Virus Research·P Seshidhar ReddyAndrew Bristol
Nov 13, 2015·Viruses·Pei-Hsin ChengHeshan Sam Zhou
Feb 23, 2019·Journal of Medical Virology·Kareem R BadrDivina D Cardoso
Nov 30, 2019·FEBS Letters·Glen Nemerow, Jane Flint
Nov 27, 2019·FEBS Letters·Paloma HidalgoRamón A Gonzalez
Dec 2, 2010·Biochemical Society Transactions·Derek Walsh
Dec 23, 2016·Cellular and Molecular Life Sciences : CMLS·Jutta SteinbergerJerry Pelletier
Jun 22, 2019·Annual Review of Biochemistry·Jerry Pelletier, Nahum Sonenberg
May 1, 2019·The Journal of Gene Medicine·Alexandra Krüger-HaagStefan Kochanek
Nov 26, 2019·Biochemistry·Rishi Kumar MishraTanweer Hussain

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