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Biochem J. Mar 15, 2002; 362(Pt 3): 539–544.
PMCID: PMC1222416

Crystal structures of 7-methylguanosine 5'-triphosphate (m(7)GTP)- and P(1)-7-methylguanosine-P(3)-adenosine-5',5'-triphosphate (m(7)GpppA)-bound human full-length eukaryotic initiation factor 4E: biological importance of the C-terminal flexible region.

Abstract

The crystal structures of the full-length human eukaryotic initiation factor (eIF) 4E complexed with two mRNA cap analogues [7-methylguanosine 5'-triphosphate (m(7)GTP) and P(1)-7-methylguanosine-P(3)-adenosine-5',5'-triphosphate (m(7)GpppA)] were determined at 2.0 A resolution (where 1 A=0.1 nm). The flexibility of the C-terminal loop region of eIF4E complexed with m(7)GTP was significantly reduced when complexed with m(7)GpppA, 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.

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Selected References

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  • Muthukrishnan S, Both GW, Furuichi Y, Shatkin AJ. 5'-Terminal 7-methylguanosine in eukaryotic mRNA is required for translation. Nature. 1975 May 1;255(5503):33–37. [PubMed]
  • Shatkin AJ. Capping of eucaryotic mRNAs. Cell. 1976 Dec;9(4 Pt 2):645–653. [PubMed]
  • Haghighat A, Sonenberg N. eIF4G dramatically enhances the binding of eIF4E to the mRNA 5'-cap structure. J Biol Chem. 1997 Aug 29;272(35):21677–21680. [PubMed]
  • Morino S, Imataka H, Svitkin YV, Pestova TV, Sonenberg N. Eukaryotic translation initiation factor 4E (eIF4E) binding site and the middle one-third of eIF4GI constitute the core domain for cap-dependent translation, and the C-terminal one-third functions as a modulatory region. Mol Cell Biol. 2000 Jan;20(2):468–477. [PMC free article] [PubMed]
  • Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK. Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP. Cell. 1997 Jun 13;89(6):951–961. [PubMed]
  • Matsuo H, Li H, McGuire AM, Fletcher CM, Gingras AC, Sonenberg N, Wagner G. Structure of translation factor eIF4E bound to m7GDP and interaction with 4E-binding protein. Nat Struct Biol. 1997 Sep;4(9):717–724. [PubMed]
  • Morino S, Hazama H, Ozaki M, Teraoka Y, Shibata S, Doi M, Ueda H, Ishida T, Uesugi S. Analysis of the mRNA cap-binding ability of human eukaryotic initiation factor-4E by use of recombinant wild-type and mutant forms. Eur J Biochem. 1996 Aug 1;239(3):597–601. [PubMed]
  • Brünger AT, Adams PD, Clore GM, DeLano WL, Gros P, Grosse-Kunstleve RW, Jiang JS, Kuszewski J, Nilges M, Pannu NS, et al. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905–921. [PubMed]
  • Nagai K. RNA-protein complexes. Curr Opin Struct Biol. 1996 Feb;6(1):53–61. [PubMed]
  • Joshi B, Cai AL, Keiper BD, Minich WB, Mendez R, Beach CM, Stepinski J, Stolarski R, Darzynkiewicz E, Rhoads RE. Phosphorylation of eukaryotic protein synthesis initiation factor 4E at Ser-209. J Biol Chem. 1995 Jun 16;270(24):14597–14603. [PubMed]
  • Fukunaga R, Hunter T. MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates. EMBO J. 1997 Apr 15;16(8):1921–1933. [PMC free article] [PubMed]
  • Sonenberg N, Gingras AC. The mRNA 5' cap-binding protein eIF4E and control of cell growth. Curr Opin Cell Biol. 1998 Apr;10(2):268–275. [PubMed]
  • Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK. Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G. Mol Cell. 1999 Jun;3(6):707–716. [PubMed]
  • Wallace AC, Laskowski RA, Thornton JM. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 1995 Feb;8(2):127–134. [PubMed]
  • Nicholls A, Sharp KA, Honig B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins. 1991;11(4):281–296. [PubMed]

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