Saccharomyces cerevisiae putative G protein, Gtr1p, which forms complexes with itself and a novel protein designated as Gtr2p, negatively regulates the Ran/Gsp1p G protein cycle through Gtr2p

Genetics. 1999 Jul;152(3):853-67.


Prp20p and Rna1p are GDP/GTP exchanging and GTPase-activating factors of Gsp1p, respectively, and their mutations, prp20-1 and rna1-1, can both be suppressed by Saccharomyces cerevisiae gtr1-11. We found that gtr1-11 caused a single amino acid substitution in Gtr1p, forming S20L, which is a putative GDP-bound mutant protein, while Gtr1p has been reported to bind to GTP alone. Consistently, gtr1-S20N, another putative GDP-bound mutant, suppressed both prp20-1 and rna1-1. On the other hand, gtr1-Q65L, a putative GTP-bound mutant, was inhibitory to prp20-1 and rna1-1. Thus, the role that Gtr1p plays in vivo appears to depend upon the nucleotide bound to it. Our data suggested that the GTP-bound Gtr1p, but not the GDP-bound Gtr1p, interacts with itself through its C-terminal tail. S. cerevisiae possesses a novel gene, GTR2, which is homologous to GTR1. Gtr2p interacts with itself in the presence of Gtr1p. The disruption of GTR2 suppressed prp20-1 and abolished the inhibitory effect of gtr1-Q65L on prp20-1. This finding, taken together with the fact that Gtr1p-S20L is a putative, inactive GDP-bound mutant, implies that Gtr1p negatively regulates the Ran/Gsp1p GTPase cycle through Gtr2p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Base Sequence
  • DNA-Binding Proteins*
  • Dose-Response Relationship, Drug
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism*
  • Guanine Nucleotide Exchange Factors
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins*
  • Mutagenesis, Site-Directed
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phylogeny
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • ran GTP-Binding Protein


  • DNA-Binding Proteins
  • Fungal Proteins
  • GSP1 protein, S cerevisiae
  • GTR2 protein, S cerevisiae
  • Gtr1 protein, S cerevisiae
  • Guanine Nucleotide Exchange Factors
  • Nuclear Proteins
  • SRM1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • GTP-Binding Proteins
  • Monomeric GTP-Binding Proteins
  • ran GTP-Binding Protein

Associated data

  • GENBANK/AB015239