The Ras protein superfamily: Evolutionary tree and role of conserved amino acids

Abstract

The Ras superfamily is a fascinating example of functional diversification in the context of a preserved structural framework and a prototypic GTP binding site. Thanks to the availability of complete genome sequences of species representing important evolutionary branch points, we have analyzed the composition and organization of this superfamily at a greater level than was previously possible. Phylogenetic analysis of gene families at the organism and sequence level revealed complex relationships between the evolution of this protein superfamily sequence and the acquisition of distinct cellular functions. Together with advances in computational methods and structural studies, the sequence information has helped to identify features important for the recognition of molecular partners and the functional specialization of different members of the Ras superfamily.

Kinetics of Interaction between ADP-ribosylation Factor-1 (Arf1) and the Sec7 Domain of Arno Guanine Nucleotide Exchange Factor, Modulation by Allosteric Factors, and the Uncompetitive Inhibitor Brefeldin A

“…As previously described (35), [⌬17]Arf1 is obtained in its GDP conformation when purified in the presence of GDP and MgCl 2 . Moreover, for the present study, the GDP-bound conformational state of the purified protein has been monitored through 1 (Table 1). In accordance with the allosteric competition between nucleotides and GEFs for the binding to G proteins as well as previous reports (9,44), the complex observed in this first experience is assumed to correspond to the free nucleotide Arf1-Arno complex (named binary complex in scheme 1) (44,45).…”

“…Low molecular weight guanine-nucleotide-binding (G) proteins of the Ras superfamily, also known as small GTPases for their GTP hydrolysis activity, are single-subunit proteins activated by diverse extracellular stimuli and implicated in a number of crucial cellular processes including cell proliferation, differentiation, apoptosis, cytoskeletal organization, cell polarity, and vesicular trafficking (1)(2)(3)(4). G proteins act as molecular switches and cycle between a GDP-bound inactive and a GTPbound active conformation that regulate their ability to interact with downstream effectors and regulatory proteins.…”

Rho GTPases as pathogen targets: Focus on curable sexually transmitted infections

“…1 These GTPases act as molecular switches, cycling between a GDP-bound form (inactive state) and a GTP-bound form (active state). This cycle is carefully regulated by more than 60 activators (guanine nucleotide exchange factors, GEFs) and over 70 inhibitors (GTPase-activating proteins, GAPs).…”

Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease

“…R -Ras2 (also known as TC21) is a GTP-binding protein that, together with R-Ras1 and R-Ras3, forms part of the R-Ras GTPase subfamily 1 . This protein is the closest relative to classical Ras GTPases according to structural similarity criteria and, in fact, is the only Ras superfamily member that shows transforming activities similar to Ras oncoproteins [2][3][4][5][6][7] .…”