title: RGK family G-domain:GTP analog complex structures and nucleotide-binding properties.
abstract: The RGK family of small G-proteins, including Rad, Gem, Rem1, and Rem2, is inducibly expressed in various mammalian tissues and interacts with voltage-dependent calcium channels and Rho kinase. Many questions remain regarding their physiological roles and molecular mechanism. Previous crystallographic studies reported RGK G-domain:guanosine di-phosphate structures. To test whether RGK proteins undergo a nucleotide-induced conformational change, we determined the crystallographic structures of Rad:GppNHp and Rem2:GppNHp to 1.7 and 1.8 Å resolutions, respectively. Also, we characterized the nucleotide-binding properties and conformations for Gem, Rad, and several structure-based mutants using fluorescence spectroscopy. The results suggest that RGK G-proteins may not behave as Ras-like canonical nucleotide-induced molecular switches. Further, the RGK proteins have differing structures and nucleotide-binding properties, which may have implications for their varied action on effectors.
authors: Department of Biochemistry, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
authors: Yehezkel
authors: Y
authors: Sasson
authors: Leehee
authors: L
authors: Navon-Perry
authors: Dan
authors: D
authors: Huppert
authors: Joel A
authors: JA
authors: Hirsch
mesh_terms: D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D031541:Fluorescence Resonance Energy Transfer; D015200:Fluoroimmunoassay; D006153:Guanosine Diphosphate / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D018631:ras Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: C084355:RRAD protein, human; D006153:Guanosine Diphosphate; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins; C517391:Rem2 protein, mouse; D018631:ras Proteins