Attributes and analysis of Rab-related and Ras-like GTPases. (A) Relevant structural features of Rab-related GTPases. The structure shown is that of Sec4 bound to a GTP analogue (pdb_id: 1g17). The two glycine residues proposed to function as hinges are indicated (with their α-carbon atoms displayed as spheres). Also indicated are: a conserved alanine residue, repositioning of which is proposed to facilitate nucleotide exchange by occluding the Mg++ binding site ; the conserved asparagine and aspartate residues of the guanine-binding loop; and the conserved aromatic residues of the glycine brace. (B) A contrast alignment (defined in (C)) highlighting a conserved residue position near the guanine-binding loop that (along with other conserved residues outside of the region shown) distinguishes all Ras-like GTPases (the 'foreground') from other P-loop GTPases (the 'background'). Relevant foreground and background consensus residues at this position, along with corresponding (weighted) residue frequencies, are shown directly below the alignment of representative GTPase sequences (protein names and pdb identifiers are indicated in the leftmost column). Residue frequencies are given in integer tenths where, for example, a '6' indicates that the corresponding residue occurs in 60%–70% of the sequences. (C) Schematic representation of a contrast alignment [12, 31]. A contrast alignment is the output returned by the CHAIN program's  BPPS procedure , which optimally partitions an input alignment into 'foreground' and 'background' sub-alignments such that the foreground sequences (red horizontal bars) strikingly conserve a pattern that is non-conserved in (or that contrasts with) the background sequences (gray horizontal bars) at pattern positions (blue vertical bars). The red vertical bars over pattern positions quantify the selective pressure (as previously defined ) that is imposed on the foreground relative to the background.