Structural effects of the binding of GTP to the wild-type and oncogenic forms of the ras-gene-encoded p21 proteins

Regina Monaco, James M. Chen, Fred K. Friedman, Paul Brandt-Rauf, Denise Chung, Matthew R. Pincus

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19 Scopus citations


Molecular dynamics calculations have been performed to determine the average structures of ras-gene-encoded p21 proteins bound to GTP, i.e., the normal (wild-type) protein and two oncogenic forms of this protein, the Val 12- and Leu 61-p21 proteins. We find that the average structures for all of these proteins exhibit low coordinate fluctuations (which are highest for the normal protein), indicating convergence to specific structures. From previous dynamics calculations of the average structures of these proteins bound to GDP, major regional differences were found among these proteins (Monaco et al. (1995), J. Protein Chem., in press). We now find that the average structures of the oncogenic proteins are more similar to one another when the proteins are bound to GTP than when they are bound to GDP (Monaco et al. (1995), J. Protein Chem., in press). However, they still differ in structure at specific amino acid residues rather than in whole regions, in contradistinction to the results found for the p21-GDP complexes. Two exceptions are the regions 25-32, in an α-helical region, and 97-110. The two oncogenic (Val 12- and Leu 61-) proteins have similar structures which differ significantly in the region of residues 97-110. This region has recently been identified as being critical in the interaction of p21 with kinase target proteins. The differences in structure between the oncogenic proteins suggest the existence of more than one oncogenic form of the p21 protein that can activate different signaling pathways.

Original languageEnglish
Pages (from-to)721-730
Number of pages10
JournalJournal of Protein Chemistry
Issue number8
StatePublished - Nov 1995
Externally publishedYes


  • GTP
  • Oncogenic p21 proteins
  • changes in conformation
  • effector domains
  • molecular dynamics


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