Crystal structures of nucleotide exchange intermediates in the eEF1A-eEF1Balpha complex

Nat Struct Biol. 2001 Jun;8(6):531-4. doi: 10.1038/88598.

Abstract

In the elongation cycle of protein biosynthesis, the nucleotide exchange factor eEF1Balpha catalyzes the exchange of GDP bound to the G-protein, eEF1A, for GTP. To obtain more information about the recently solved eEF1A-eEF1Balpha structure, we determined the structures of the eEF1A-eEF1Balpha-GDP-Mg2+, eEF1A-eEF1Balpha-GDP and eEF1A-eEF1Balpha-GDPNP complexes at 3.0, 2.4 and 2.05 A resolution, respectively. Minor changes, specifically around the nucleotide binding site, in eEF1A and eEF1Balpha are consistent with in vivo data. The base, sugar and alpha-phosphate bind as in other known nucleotide G-protein complexes, whereas the beta- and gamma-phosphates are disordered. A mutation of Lys 205 in eEF1Balpha that inserts into the Mg2+ binding site of eEF1A is lethal. This together with the structures emphasizes the essential role of Mg2+ in nucleotide exchange in the eEF1A-eEF1Balpha complex.

Publication types

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

MeSH terms

  • Amino Acid Substitution / genetics
  • Binding Sites
  • Carbohydrate Metabolism
  • Crystallography, X-Ray
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / metabolism*
  • Lysine / genetics
  • Lysine / metabolism
  • Magnesium / metabolism
  • Models, Molecular
  • Mutation / genetics
  • Orotic Acid / analogs & derivatives
  • Orotic Acid / pharmacology
  • Peptide Elongation Factor 1 / chemistry*
  • Peptide Elongation Factor 1 / genetics
  • Peptide Elongation Factor 1 / metabolism*
  • Protein Conformation
  • Yeasts / chemistry*
  • Yeasts / drug effects
  • Yeasts / genetics
  • Yeasts / metabolism

Substances

  • Peptide Elongation Factor 1
  • Guanosine Diphosphate
  • Orotic Acid
  • 5-fluoroorotic acid
  • Magnesium
  • Lysine

Associated data

  • PDB/1G7C
  • PDB/1IJE
  • PDB/1IJF