Evolution of a Signaling Nexus Constrained by Protein Interfaces and Conformational States
Figure 3
Alignment of select human Gα subtypes highlighting invariant and class-distinctive sites.
Invariant residues are conserved across all 4 Gα classes (INV: colored dark gray) while class-distinctive sites are conserved across 3 of the 4 Gα classes to a non-distinctive (η: colored light gray) amino acid value. At class-distinctive sites, distinctive (∂) amino acid values are allowed in the remaining class but are not required to be absolutely conserved within all sequences in the distinctive Gα class, thus allowing for subclass variation at that site. Some sites are identified as class-distinctive based on variation in a single non-human sequence. See Table S2 to identify sequences where ∂ occurs. d sites lie within 5 Å of a distinctive site but are conserved in 2 classes (see Table S2 and Table S3 for summaries). ∂ amino acid values are colored according to Gα class and noted above the alignment: ‘I’ = G(io) site (green); ‘Q’ = G(q) site (magenta); ‘S’ = G(s) site (blue); ‘2’ = G(12) site (yellow orange) and ‘d’ = d site. Functional regions are indicated below the alignment, including regions important for coupling to the receptor (GPCR), guanine-nucleotide-dependent conformational change (switches I, II, III) and nucleotide binding (P-loop, NKxD, TCAT). Also noted below the alignment (‘*’) are distinctive sites discussed in more detail in results. Distinctive sites for all 4 Gα classes were defined using 58 mammalian Gα sequences from 14 subtypes and a reduced amino acid alphabet (Materials and Methods).