title: Molecular dynamics simulations of the Ras:Raf and Rap:Raf complexes.
abstract: The protein Raf is an immediate downstream target of Ras in the MAP kinase signalling pathway. The complex of Ras with the Ras-binding domain (RBD) of Raf has been modelled by homology to the (E30D,K31E)-Rap1A:RBD complex, and both have been subjected to multiple molecular dynamics simulations in solution. While both complexes are stable, several rearrangements occur in the Ras:RBD simulations: the RBD loop 100-109 moves closer to Ras, Arg73 in the RBD moves towards Ras to form a salt bridge with Ras-Asp33, and Loop 4 of the Ras switch II region shifts upwards toward the RBD. The Ras:RBD interactions (including the RBD-Arg73 interaction) are consistent with available NMR and mutagenesis data on the Ras: RBD complex in solution. The Ras switch II region does not interact directly with the RBD, although indirect interactions exist through the effector domain and bridging water molecules. No large-scale RBD motion is seen in the Ras:RBD complex, compared to the Rap:RBD complex, to suggest an allosteric activation of Raf by Ras. This may be because the Raf kinase domain (whose structure is unknown) is not included in the model.
authors: Laboratoire de Biologie Structurale (CNRS), IGBMC Illkirch (C.U. de Strasbourg), France.
authors: J
authors: J
authors: Zeng
authors: H R
authors: HR
authors: Treutlein
authors: T
authors: T
authors: Simonson
mesh_terms: D000595:Amino Acid Sequence; D019204:GTP-Binding Proteins / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D019908:Proto-Oncogene Proteins c-raf / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D020668:rap GTP-Binding Proteins; D018631:ras Proteins / Q000737:chemistry*
chemical_list: D019908:Proto-Oncogene Proteins c-raf; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins; D018631:ras Proteins