Structural differences between a ras oncogene protein and the normal protein.

L A Tong; A M de Vos; M V Milburn; J Jancarik; S Noguchi; S Nishimura; K Miura; E Ohtsuka; S H Kim

doi:10.1038/337090a0

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Structural differences between a ras oncogene protein and the normal protein.

L A Tong·A M de Vos·M V Milburn·J Jancarik·S Noguchi·S Nishimura·K Miura·E Ohtsuka·S H Kim

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Abstract

One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene. To understand the structural reasons behind cell transformation arising from this single amino acid substitution, we have determined the crystal structure of the GDP-bound form of the mutant protein, p21(Val-12), encoded by this oncogene. We report here the overall structure of p21(Val-12) at 2.2 A resolution and compare it with the structure of the normal c-Ha-ras protein. One of the major differences is that the loop of the transforming ras protein that binds the beta-phosphate of the guanine nucleotide is enlarged. Such a change in the 'catalytic site' conformation could explain the reduced GTPase activity of the mutant, which keeps the protein in the GTP bound 'signal on' state for a prolonged period time, ultimately causing cell transformation.

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Crystallography Models, Molecular Molecular Structure Mutation Nucleic Acid Conformation Proto-Oncogene Proteins Proto-Oncogene Proteins p21(ras)Journal Article 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.

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L A Tong, A M de Vos, M V Milburn, J Jancarik, S Noguchi, S Nishimura, K Miura, E Ohtsuka, S H Kim. 1989-01-05. Structural differences between a ras oncogene protein and the normal protein.. https://doi.org/10.1038/337090a0

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