Three-dimensional structure and properties of wild-type and mutant H-ras-encoded p21

Ciba Found Symp. 1993:176:6-21; discussion 21-7. doi: 10.1002/9780470514450.ch2.

Abstract

Ras (or p21) is the product of the ras proto-oncogene and is believed to be involved in growth-promoting signal transduction. The structure of the guanine nucleotide-binding domain of H-Ras (or p21H-ras) in the triphosphate conformation was determined at very high resolution (1.4 A). All the binding interactions between protein and Gpp[NH]p and Mg2+ can be resolved in great detail. The region around amino acids 61-65 is flexible and exists in two conformations, one of which seems to be important for catalysis. The properties and structures of several oncogenic and non-oncogenic mutant forms of Ras have also been determined. Since the structure of the GDP-bound form is also known, the nature of the conformational change from the GTP-bound to the GDP-bound form can be inferred from the 3-D structure. A mechanism for the intrinsic GTP hydrolysis has been proposed. Its implications for the GAP-stimulated GTPase reaction is discussed in the light of recent kinetic and mutational experiments.

Publication types

  • Review

MeSH terms

  • Animals
  • GTP Phosphohydrolases / metabolism
  • Genes, ras*
  • Genetic Code
  • Humans
  • Mutation*
  • Protein Conformation
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins p21(ras) / chemistry*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • GTP Phosphohydrolases
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)