X-ray studies of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP

Nucleic Acids Symp Ser. 1997;(36):8-11.

Abstract

The X-ray structure of the eukaryotic translation initiation factor 4E (eIF4E), bound to 7-methyl-GDP, has been determined at 2.2A 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. Additional protein-ligand interactions include salt bridges and hydrogen bonds, plus water-mediated hydrogen bonds. The observed mode of 5' m-RNA cap recognition is almost certainly conserved among all known eIF4Es.

Publication types

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

MeSH terms

  • Crystallography, X-Ray
  • Dinucleoside Phosphates / metabolism
  • Eukaryotic Initiation Factor-4E
  • Guanosine Diphosphate / analogs & derivatives*
  • Guanosine Diphosphate / chemistry
  • Guanosine Diphosphate / metabolism
  • Hydrogen Bonding
  • Hydrogen-Ion Concentration
  • Models, Molecular
  • Peptide Initiation Factors / chemistry*
  • Peptide Initiation Factors / metabolism
  • Protein Conformation
  • Protein Structure, Secondary
  • RNA Caps / metabolism

Substances

  • Dinucleoside Phosphates
  • Eukaryotic Initiation Factor-4E
  • Peptide Initiation Factors
  • RNA Caps
  • 7-methylguanosine 5'-diphosphate
  • Guanosine Diphosphate
  • 7-methyl-diguanosine triphosphate