Crystal structures of 7-methylguanosine 5′-triphosphate (m7GTP)- and P1-7-methylguanosine-P3-adenosine-5′,5′-triphosphate (m7GpppA)-bound human full-length eukaryotic initiation factor 4E: biological importance of the C-terminal flexible region

2002 ◽  
Vol 362 (3) ◽  
pp. 539-544 ◽  
Author(s):  
Koji TOMOO ◽  
Xu SHEN ◽  
Koumei OKABE ◽  
Yoshiaki NOZOE ◽  
Shoichi FUKUHARA ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Biological Function ◽  
Full Length ◽  
Initiation Factor ◽  
Regulatory Function ◽  
Structural Basis ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E ◽  
Loop Region ◽  
Terminal Loop

The crystal structures of the full-length human eukaryotic initiation factor (eIF) 4E complexed with two mRNA cap analogues [7-methylguanosine 5′-triphosphate (m7GTP) and P1-7-methylguanosine-P3-adenosine-5′,5′-triphosphate (m7GpppA)] were determined at 2.0Å resolution (where 1Å = 0.1nm). The flexibility of the C-terminal loop region of eIF4E complexed with m7GTP was significantly reduced when complexed with m7GpppA, suggesting the importance of the second nucleotide in the mRNA cap structure for the biological function of eIF4E, especially the fixation and orientation of the C-terminal loop region, including the eIF4E phosphorylation residue. The present results provide the structural basis for the biological function of both N- and C-terminal mobile regions of eIF4E in translation initiation, especially the regulatory function through the switch-on/off of eIF4E-binding protein—eIF4E phosphorylation.

scholarly journals Phosphorylation of eukaryotic initiation factor 4E (eIF4E) at Ser209 is not required for protein synthesis in vitro and in vivo

2001 ◽  
Vol 268 (20) ◽  
pp. 5375-5385 ◽  
Author(s):  
Linda McKendrick ◽  
Simon J. Morley ◽  
Virginia M. Pain ◽  
Rosemary Jagus ◽  
Bhavesh Joshi
Keyword(s):  
Protein Synthesis ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E

Thermodynamics of Molecular Recognition of mRNA 5′ Cap by Yeast Eukaryotic Initiation Factor 4E

2011 ◽  
Vol 115 (27) ◽  
pp. 8746-8754 ◽  
Author(s):  
Katarzyna Kiraga-Motoszko ◽  
Anna Niedzwiecka ◽  
Anna Modrak-Wojcik ◽  
Janusz Stepinski ◽  
Edward Darzynkiewicz ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E

Tissue Distribution, Genomic Structure, and Chromosome Mapping of Mouse and Human Eukaryotic Initiation Factor 4E-Binding Proteins 1 and 2

Genomics ◽  
1996 ◽  
Vol 38 (3) ◽  
pp. 353-363 ◽  
Author(s):  
Kyoko Tsukiyama-Kohara ◽  
Silvia M. Vidal ◽  
Anne-Claude Gingras ◽  
Thomas W. Glover ◽  
Samir M. Hanash ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Binding Proteins ◽  
Genomic Structure ◽  
Chromosome Mapping ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E

scholarly journals Cap-binding protein (eukaryotic initiation factor 4E) and 4E-inactivating protein BP-1 independently regulate cap-dependent translation.

1996 ◽  
Vol 16 (10) ◽  
pp. 5450-5457 ◽  
Author(s):  
D Feigenblum ◽  
R J Schneider
Keyword(s):  
Heat Shock ◽  
Translation Initiation ◽  
Binding Protein ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Metaphase Arrest ◽  
Animal Cells ◽  
Eukaryotic Initiation Factor 4E ◽  
Dependent Protein

Cap-dependent protein synthesis in animal cells is inhibited by heat shock, serum deprivation, metaphase arrest, and infection with certain viruses such as adenovirus (Ad). At a mechanistic level, translation of capped mRNAs is inhibited by dephosphorylation of eukaryotic initiation factor 4E (eIF-4E) (cap-binding protein) and its physical sequestration with the translation repressor protein BP-1 (PHAS-I). Dephosphorylation of BP-I blocks cap-dependent translation by promoting sequestration of eIF-4E. Here we show that heat shock inhibits translation of capped mRNAs by simultaneously inducing dephosphorylation of eIF-4E and BP-1, suggesting that cells might coordinately regulate translation of capped mRNAs by impairing both the activity and the availability of eIF-4E. Like heat shock, late Ad infection is shown to induce dephosphorylation of eIF-4E. However, in contrast to heat shock, Ad also induces phosphorylation of BP-1 and release of eIF-4E. BP-1 and eIF-4E can therefore act on cap-dependent translation in either a mutually antagonistic or cooperative manner. Three sets of experiments further underscore this point: (i) rapamycin is shown to block phosphorylation of BP-1 without inhibiting dephosphorylation of eIF-4E induced by heat shock or Ad infection, (ii) eIF-4E is efficiently dephosphorylated during heat shock or Ad infection regardless of whether it is in a complex with BP-1, and (iii) BP-1 is associated with eIF-4E in vivo regardless of the state of eIF-4E phosphorylation. These and other studies establish that inhibition of cap-dependent translation does not obligatorily involve sequestration of eIF-4E by BP-1. Rather, translation is independently regulated by the phosphorylation states of eIF-4E and the 4E-binding protein, BP-1. In addition, these results demonstrate that BP-1 and eIF-4E can act either in concert or in opposition to independently regulate cap-dependent translation. We suggest that independent regulation of eIF-4E and BP-1 might finely regulate the efficiency of translation initiation or possibly control cap-dependent translation for fundamentally different purposes.

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