J Mol Biol 2010 Jun 31;399(3):422-35. Epub 2010 Mar 31.
Physikalische Chemie I, Fakultät für Chemie und Biochemie, Ruhr-Universität-Bochum, Universitätstr. 150, 44780 Bochum, Germany.
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Oncogene 1995 Aug;11(3):447-54
Dept. Mole. Biology, Bristol Myers & Squibb Research Institute, Princeton, New Jersey 08543, USA.
Ras proteins function through the formation of specific complexes with Raf-1, B-raf, PI-3 kinase and RalGDS. These interactions all require Ras-GTP with an intact effector binding domain (Switch I region). We have examined the requirements of the Switch II region (amino acids 60-72) for the production of stable interactions between Ras and its downstream effectors. Read More
J Biol Chem 2005 Sep 30;280(35):31267-75. Epub 2005 Jun 30.
Division of Molecular Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Although some members of Ras family small GTPases, including M-Ras, share the primary structure of their effector regions with Ras, they exhibit vastly different binding properties to Ras effectors such as c-Raf-1. We have solved the crystal structure of M-Ras in the GDP-bound and guanosine 5'-(beta,gamma-imido)triphosphate (Gpp(NH)p)-bound forms. The overall structure of M-Ras resembles those of H-Ras and Rap2A, except that M-Ras-Gpp(NH)p exhibits a distinctive switch I conformation, which is caused by impaired intramolecular interactions between Thr-45 (corresponding to Thr-35 of H-Ras) of the effector region and the gamma-phosphate of Gpp(NH)p. Read More
Biochemistry 2006 Jan;45(1):42-50
Institute of Physical and Theoretical Chemistry and Center for Biomolecular Magnetic Resonance, J. W. Goethe University of Frankfurt, D-60439 Frankfurt, Germany.
The guanine nucleotide binding protein Ras plays a central role as molecular switch in cellular signal transduction. Ras cycles between a GDP-bound "off" state and a GTP-bound "on" state. Specific oncogenic mutations in the Ras protein are found in up to 30% of all human tumors. Read More
J Mol Biol 2004 Sep;342(3):1033-40
Universität Regensburg, Institut für Biophysik und physikalische Biochemie, Postfach, D-93040 Regensburg, Germany.
Cycling between a GTP bound "on" state and a GDP bound "off" state, guanine nucleotide-binding (GNB) proteins act as molecular switches. The switching process and the interaction with effectors, GTPase-activating proteins, and guanosine nucleotide-exchange factors is accompanied by pronounced conformational changes of the switch regions of the GNB proteins. The aim of the present contribution is to correlate conformational changes observed by liquid-state NMR with solid-state (31)P NMR data and with the results of X-ray crystallography. Read More