Universal allosteric mechanism for Gα activation by GPCRs
By T. Flock, C. Ravarani, Dawei Sun, A. Venkatakrishnan, M. Kayikci, C. Tate, D. Veprintsev, M. Babu. Nature, 2015
326 citations recorded by the source corpus.
G protein-coupled receptors (GPCRs) allosterically activate heterotrimeric G proteins and trigger GDP release. Given that there are ∼800 human GPCRs and 16 different Gα genes, this raises the question of whether a universal allosteric mechanism governs Gα activation. Here we show that different GPCRs interact with and activate Gα proteins through a highly conserved mechanism. Comparison of Gα with the small G protein Ras reveals how the evolution of short segments that undergo disorder-to-order transitions can decouple regions important for allosteric activation from receptor binding specificity. This might explain how the GPCR–Gα system diversified rapidly, while conserving the allosteric activation mechanism.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/20ba7ceccf717b056a036754be93ca247430de9a
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Citations in the corpus
- Pharmacogenomics of GPCR Drug Targets (2018, unknown): “…by affecting allosteric sites, effector selectivity sites, receptor stability, and oligomerization (Congreve et al., 2017; Costa-Neto et al., 2016; Flock et al., 2015, 2017; Gahbauer Cell 172 , 41–54, January 11, 2018 43 and Bo¨ckmann, 2016; Katritch et al., 2014; Venkatakrishnan et al., 2013,…”
- Exploring the free-energy landscape of GPCR activation (2018, background): “Finally, the C terminus of the α-subunit (often referred to as α5) was modeled in two conformations, termed “in” and “out” herein [standing for in the activated receptor cavity and out of the receptor cavity; described as disorder-to-order for out-to-in elsewhere (30)], based on the original conform”
- Exploiting sequence and stability information for directing nanobody stability engineering (2017, methodology): “Residue contact networks for each single protein chain and the consensus networks (structurally conserved residue contacts in a set of structures) for all dromedary and llama nanobodies were calculated as previously described [56].”