Figure 5.

Ras proteins of Saccharomyces cerevisiae and Candida albicans.A, post-translational modifications of Ras proteins and their subcellular localization. Ras proteins are produced in the cytoplasm. The N-terminal Met is removed almost immediately by methionine aminopeptidase and a farnesyl chain is added to the Cys residue of the C-terminal CAAX (C: Cys, A: aliphatic amino acids, X: the C-terminal amino acid) domain by a farnesyltransferase. The AAX motif is then proteolytically cleaved by an endopeptidase, Rce1, and the new C-terminal -COOH generated is converted to an ester by the action of an isoprenylcysteine methyltransferase (ICMT). Finally, a palmitoyltransferase enzyme complex adds a palmitoyl chain to an adjacent Cys and the protein is transported to the PM. B, domain organization of mature ScRas2 and CaRas1. Mature Ras proteins contain five well-conserved G boxes at their N-terminus that are required for GTP binding. The G1 and G2 motifs bind Mg⁺²-bound β and γ P_i, respectively. The crucial Gln required for GTPase activity is located in the G3 motif. G4 and G5 motifs bind guanine and the ribose sugar. Nucleotide exchange after GEF binding induces large conformational changes in switch I and switch II regions. ScRas2/CaRas1 also have hypervariable regions (HVR) whose sequences are poorly conserved. The C-terminal CAAX domain and the residues on which farnesylation and palmitoylation occur are specifically shown.