Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP

Cell. 1997 Jun 13;89(6):951-61. doi: 10.1016/s0092-8674(00)80280-9.


The X-ray structure of the eukaryotic translation initiation factor 4E (eIF4E), bound to 7-methyl-GDP, has been determined at 2.2 A resolution. eIF4E recognizes 5' 7-methyl-G(5')ppp(5')N mRNA caps during the rate-limiting initiation step of translation. The protein resembles a cupped hand and consists of a curved, 8-stranded antiparallel beta sheet, backed by three long alpha helices. 7-methyl-GDP binds in a narrow cap-binding slot on the molecule's concave surface, where 7-methyl-guanine recognition is mediated by base sandwiching between two conserved tryptophans, plus formation of three hydrogen bonds and a van der Waals contact between its N7-methyl group and a third conserved tryptophan. The convex dorsal surface of the molecule displays a phylogenetically conserved hydrophobic/acidic portion, which may interact with other translation initiation factors and regulatory proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites / physiology
  • Conserved Sequence*
  • Crystallography
  • Escherichia coli / genetics
  • Eukaryotic Cells / physiology
  • Eukaryotic Initiation Factor-4E
  • Guanosine Diphosphate / analogs & derivatives*
  • Guanosine Diphosphate / metabolism
  • Methylation
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Peptide Initiation Factors / chemistry*
  • Peptide Initiation Factors / genetics*
  • Peptide Initiation Factors / metabolism
  • Protein Biosynthesis / physiology
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA Cap Analogs / metabolism*
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism*
  • Sequence Homology, Amino Acid


  • Eukaryotic Initiation Factor-4E
  • Peptide Initiation Factors
  • RNA Cap Analogs
  • RNA, Messenger
  • 7-methylguanosine 5'-diphosphate
  • Guanosine Diphosphate