Journal of Protein Chemistry

, Volume 15, Issue 6, pp 511–518

Computed three-dimensional structures for theras-binding domain of theraf-p74 protein complexed withras-p21 and with its suppressor protein, rap-1A

  • James M. Chen
  • Spero Manolatos
  • Paul W. Brandt-Rauf
  • Randall B. Murphy
  • Regina Monaco
  • Matthew R. Pincus
Article
  • 24 Downloads

Abstract

The three-dimensional structures of theras-p21 protein and its protein inhibitor, rap-1A, have been computed bound to theras-binding domain, RBD (residues 55–131), of theraf-p74 protein, a critical target protein ofras-p21 in theras-induced mitogenic signal transduction pathway. The coordinates of RBD have been reconstructed from the stereoview of an X-ray crystal structure of this domain bound to rap-1A and have been subjected to energy minimization. The energy-minimized structures of bothras- p21 and rap-1A, obtained in previous studies, have been docked against RBD, using the stereo figure of the RBD-rap-1A complex, based on a six-step procedure. The final energy-minimized structure of rap-1A-RBD is identical to the X-ray crystal structure. Comparison of theras-p21- and rap-1A-RBD complexes reveals differences in the structures of effector domains ofras-p21 and rap-1a, including residues 32–47, a domain that directly interacts with RBD, 60–66, 96–110, involved in the interaction ofras-p21 withjun kinase (JNK) andjun protein, and 115–126, involved in the interaction of p21 with JNK. The structure of the RBD remained the same in both complexes with the exception of small deviations in itsβ-2 binding loop (residues 63–71) and residues 89–91, also involved in binding to rap-1A. The results suggest that the binding of these two proteins to RBD may allow them to interact with other cellular target proteins such as JNK andjun.

Key words

ras-binding domain ofraf-p74 (RBD) rap-1A- andras-p21-RBD complexes energy-minimized structures structural differences, effector domains 

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Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • James M. Chen
    • 1
  • Spero Manolatos
    • 2
  • Paul W. Brandt-Rauf
    • 3
    • 4
  • Randall B. Murphy
    • 5
  • Regina Monaco
    • 5
  • Matthew R. Pincus
    • 6
  1. 1.Dupont Agricultural Products, Stein-Haskell Research CenterNewark
  2. 2.Department of Radiation OncologyVeterans Affairs Medical Center BrooklynNew York
  3. 3.Division of Environmental SciencesColumbia College of Physicians and SurgeonsNew York
  4. 4.Department of ChemistryNew York UniversityNew York
  5. 5.Department of Pathology and Laboratory MedicineVeterans Affairs Medical CenterBrooklyn
  6. 6.Department of PathologySUNY Health Science CenterBrooklyn11203

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