J Mol Biol 2003 Jul;330(4):891-913
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
J Mol Biol 2004 Jul;340(5):1039-58
Max-Planck-Institut für Molekulare Physiologie, Abteilung Strukturelle Biologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Many cellular functions are based on the interaction and crosstalk of various signaling proteins. Among these, members of the Ras family of small GTP-binding proteins are important for communicating signals into different pathways. In order to answer the question of how binding affinity and specificity is achieved, we analyzed binding energetics on the molecular level, with reference to the available structural data. Read More
Protein Sci 1999 Jan;8(1):50-64
Laboratoire de Biologie Structurale (C.N.R.S), I.G.B.M.C, Illkirch (C.U. de Strasbourg), France.
Binding of the protein Raf to the active form of Ras promotes activation of the MAP kinase signaling pathway, triggering cell growth and differentiation. Raf/Arg89 in the center of the binding interface plays an important role determining Ras-Raf binding affinity. We have investigated experimentally and computationally the Raf-R89K mutation, which abolishes signaling in vivo. Read More
J Phys Chem B 2010 Nov 22;114(46):15331-44. Epub 2010 Oct 22.
Department of Chemistry and Biochemistry and Institute for Cell and Molecular Biology, The University of Texas at Austin, 1 University Station, A5300, Austin, Texas 78712, USA.
Electrostatic fields at the interface of the Ras binding domain of the protein Ral guanine nucleotide dissociation stimulator (RalGDS) with the structurally analogous GTPases Ras and Rap1A were measured with vibrational Stark effect (VSE) spectroscopy. Eleven residues on the surface of RalGDS that participate in this protein-protein interaction were systematically mutated to cysteine and subsequently converted to cyanocysteine in order to introduce a nitrile VSE probe in the form of the thiocyanate (SCN) functional group. The measured SCN absorption energy on the monomeric protein was compared with solvent-accessible surface area (SASA) calculations and solutions to the Poisson-Boltzmann equation using Boltzmann-weighted structural snapshots from molecular dynamics simulations. Read More
J Biol Chem 1998 Mar;273(13):7737-42
Cellular Signaling Laboratory, Institute of Physical and Chemical Research (RIKEN), Hirosawa 2-1, Wako-shi, Saitama 351-01, Japan.
The Ras and Rap1A proteins can bind to the Raf and RalGDS families. Ras and Rap1A have Glu and Lys, respectively, at position 31. In the present study, we analyzed the effects of mutating the Glu at position 31 of the c-Ha-Ras protein to Asp, Ala, Arg, and Lys on the interactions with Raf-1 and RalGDS. Read More