RGK family G-domain:GTP analog complex structures and nucleotide-binding properties

J Mol Biol. 2011 Oct 21;413(2):372-89. doi: 10.1016/j.jmb.2011.08.017. Epub 2011 Aug 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Fluorescence Resonance Energy Transfer
  • Fluoroimmunoassay
  • Guanosine Diphosphate / chemistry*
  • Guanosine Diphosphate / metabolism*
  • Humans
  • Mice
  • Models, Chemical
  • Models, Molecular
  • Monomeric GTP-Binding Proteins / chemistry*
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Mutagenesis, Site-Directed
  • Mutation / genetics
  • Protein Binding
  • Protein Conformation
  • ras Proteins / chemistry*
  • ras Proteins / genetics
  • ras Proteins / metabolism*


  • RRAD protein, human
  • Guanosine Diphosphate
  • GEM protein, human
  • Monomeric GTP-Binding Proteins
  • Rem2 protein, mouse
  • ras Proteins

Associated data

  • PDB/3Q72
  • PDB/3Q7P
  • PDB/3Q7Q
  • PDB/3Q85