Structure of the Ras-binding domain of c-Raf-1 as determined by NMR spectroscopy and identification of the region that interacts with Ras.
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.
Emerson
S D
SD
Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Madison
V S
VS
Palermo
R E
RE
Waugh
D S
DS
Scheffler
J E
JE
Tsao
K L
KL
Kiefer
S E
SE
Liu
S P
SP
Fry
D C
DC
D001665:Binding Sites; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D014452:Ubiquitins / Q000737:chemistry; D018631:ras Proteins / Q000737:chemistry* / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D014452:Ubiquitins; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins