Structure-function studies of the G-domain from human gem, a novel small G-protein

FEBS Lett. 2006 Oct 30;580(25):5959-64. doi: 10.1016/j.febslet.2006.09.067. Epub 2006 Oct 6.

Abstract

Gem, a member of the Rad,Gem/Kir subfamily of small G-proteins, has unique sequence features. We report here the crystallographic structure determination of the Gem G-domain in complex with nucleotide to 2.4 A resolution. Although the basic Ras protein fold is maintained, the Gem switch regions emphatically differ from the Ras paradigm. Our ensuing biochemical characterization indicates that Gem G-domain markedly prefers GDP over GTP. Two known functions of Gem are distinctly affected by spatially separated clusters of mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Crystallography, X-Ray
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins / chemistry*
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Mutagenesis, Site-Directed
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Static Electricity
  • rho-Associated Kinases

Substances

  • Intracellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • GEM protein, human
  • Monomeric GTP-Binding Proteins