1. Structure of the Ras-binding domain of c-Raf-1 as determined by NMR spectroscopy and identification of the region that interacts with Ras.
- Author
-
Emerson SD, Madison VS, Palermo RE, Waugh DS, Scheffler JE, Tsao KL, Kiefer SE, Liu SP, and Fry DC
- Subjects
- Binding Sites, Humans, Magnetic Resonance Spectroscopy, Models, Molecular, Protein Binding, Protein Serine-Threonine Kinases metabolism, Protein Structure, Tertiary, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-raf, Ubiquitins chemistry, ras Proteins metabolism, Protein Serine-Threonine Kinases chemistry, Proto-Oncogene Proteins chemistry, ras Proteins chemistry
- Abstract
The structure of the Ras-binding domain of human c-Raf-1 (residues 55 to 132) as determined in solution by NMR spectroscopy is presented. It consists of a five-stranded beta-sheet, a twelve residue alpha-helix, and an additional one-turn helix. The fold belongs to a known family whose members include ubiquitin and protein G. The surface of Raf55-132 that interacts with Ras has been identified by resonance perturbation mapping. The binding site is a spatially contiguous patch comprised of the two-N-terminal beta-strands, the loop between them, and the C-terminal end of the alpha-helix. A model of the Raf-Ras complex is presented, which was derived by analogy to the complex between protein G and a Fab fragment of IgG. In the model, edge beta-strands of each protein align in an antiparallel orientation, forming a unified beta-sheet, and side chains from both proteins are able to participate in ionic and hydrophobic interactions at the interface.
- Published
- 1996