Abstract
By comparing the average structures, computed using molecular dynamics, of the ras-binding domain of raf (RBD) bound to activated wild-type ras-p21 and its homologous inhibitory protein, rap-1A, we formerly identified three domains of the RBD that changed conformation between the two complexes, residues 62–76, 97–110, and 111–121. We found that one synthetic peptide, corresponding to RBD residues 97–110, selectively inhibited oncogenic ras-p21-induced oocyte maturation. In this study, we performed molecular dynamics on the Val 12-ras-p21-RBD complex and compared its average structure with that for the wild-type protein. We find that there is a large displacement of a loop involving these residues when the structures of the two complexes are compared. This result corroborates our former finding that the RBD 97–110 peptide inhibits only signal transduction by oncogenic ras-p21 and suggests that oncogenic p21 uses this loop to interact with raf in a unique manner.
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Chen, J.M., Rijhwani, K., Friedman, F.K. et al. Identification, Using Molecular Dynamics, of an Effector Domain of the ras-Binding Domain of the raf-p74 Protein That Is Uniquely Involved in Oncogenic ras-p21 Signaling. J Protein Chem 19, 545–551 (2000). https://doi.org/10.1023/A:1007127700199
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DOI: https://doi.org/10.1023/A:1007127700199