Journal article
Conformational effects of substituting amino acids for glutamine-61 on the central transforming region of the P21 proteins
Proceedings of the National Academy of Sciences - PNAS, v 84(23), pp 8375-8379
Dec 1987
PMID: 3120190
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Abstract
The low-energy conformations for a series of peptides based on the sequence of the ras P21 protein from position 55 to position 67 have been computed using conformational energy analysis. These sequences differed at position 61 and contained Gln, Pro, Leu, Lys, and Arg at this position. P21 proteins with Gln, Glu, or Pro at this position do not cause cell transformation at normal levels of expression; proteins with substitutions of at least 14 other amino acids at this position (Leu, Lys, and Arg having been found in tumors in place of the normally occurring Gln-61) do cause malignant transformation of cells in culture. We find that the segments of residues 55-67 from the nontransforming proteins (Gln- or Pro-61) adopt a structure that is energetically unfavorable for the same segment with Leu, Lys, or Arg at position 61. The critical feature of this structure is an alpha-helix from residues 62 to 68. Residue 61 (Gln or Pro) adopts an extended conformation. On the other hand, the segment from transforming proteins can adopt two structures, one all alpha-helical from residue 61 to residue 68 and the other a less-regular, higher-energy structure. The segments from the normal protein can adopt the all alpha-helical structure, a finding that can explain the fact that elevated intracellular levels of the normal protein also cause cell transformation. The results of the calculations suggest that specific changes in the structure of this region can account for the oncogenic effect of the proteins in which substitutions occur.
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Details
- Title
- Conformational effects of substituting amino acids for glutamine-61 on the central transforming region of the P21 proteins
- Creators
- M R Pincus - Department of Pathology, New York University Medical Center, NY 10016P W Brandt-Rauf - Cancer CenterR P Carty - New York UniversityJ Lubowsky - New York UniversityM Avitable - New York UniversityK D Gibson - New York UniversityH A Scheraga - New York University
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 84(23), pp 8375-8379
- Publisher
- PNAS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:A1987L129600042
- Scopus ID
- 2-s2.0-0023508307
- Other Identifier
- 991019342441904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology