Year: 2010
Type: article
Abstract: Heterotrimeric G proteins act as the physical nexus between numerous receptors that respond to extracellular signals and proteins that drive the cytoplasmic response. The Gα subunit of the G protein, in particular, is highly constrained due to its many interactions with proteins that control or react to its conformational state. Various organisms contain differing sets of Gα-interacting proteins, clearly indicating that shifts in sequence and associated Gα functionality were acquired over time. These numerous interactions constrained much of Gα evolution; yet Gα has diversified, through poorly understood processes, into several functionally specialized classes, each with a unique set of interacting proteins. Applying a synthetic sequence-based approach to mammalian Gα subunits, we established a set of seventy-five evolutionarily important class-distinctive residues, sites where a single Gα class is differentiated from the three other classes. We tested the hypothesis that shifts at these sites are important for class-specific functionality. Importantly, we mapped known and well-studied class-specific functionalities from all four mammalian classes to sixteen of our class-distinctive sites, validating the hypothesis. Our results show how unique functionality can evolve through the recruitment of residues that were ancestrally functional. We also studied acquisition of functionalities by following these evolutionarily important sites in non-mammalian organisms. Our results suggest that many class-distinctive sites were established early on in eukaryotic diversification and were critical for the establishment of new Gα classes, whereas others arose in punctuated bursts throughout metazoan evolution. These Gα class-distinctive residues are rational targets for future structural and functional studies.
Source: PLoS Computational Biology
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Awards: From Plasma Membrane to Organelle: Novel Sugar Signaling through the Arabidopsis Heterotrimeric G Protein Complex, G222768804, G2973901274, SUGAR SENSING IN ARABIDOPSIS VIA ATRGS1, Decoding the phosphorylation bar code in Arabidopsis G Biased Signaling, G5812383484, 2010/AFGN Collaborative Project: The Heterotrimeric G-Protein Interactome, An Integrative Analysis of Gene Conversion, Cancer Center Support Grant
OpenAlex ID: W1992442424