Journal ArticleDOI
Multi-functionality of proteins involved in GPCR and G protein signaling: making sense of structure–function continuum with intrinsic disorder-based proteoforms
Alexander V. Fonin,April L. Darling,Irina M. Kuznetsova,Konstantin K. Turoverov,Konstantin K. Turoverov,Vladimir N. Uversky,Vladimir N. Uversky +6 more
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TLDR
The multifunctionality of GPCR–G protein system represents an illustrative example of the protein structure–function continuum, where structures of the involved proteins represent a complex mosaic of differently folded regions.Abstract:
GPCR-G protein signaling system recognizes a multitude of extracellular ligands and triggers a variety of intracellular signaling cascades in response. In humans, this system includes more than 800 various GPCRs and a large set of heterotrimeric G proteins. Complexity of this system goes far beyond a multitude of pair-wise ligand-GPCR and GPCR-G protein interactions. In fact, one GPCR can recognize more than one extracellular signal and interact with more than one G protein. Furthermore, one ligand can activate more than one GPCR, and multiple GPCRs can couple to the same G protein. This defines an intricate multifunctionality of this important signaling system. Here, we show that the multifunctionality of GPCR-G protein system represents an illustrative example of the protein structure-function continuum, where structures of the involved proteins represent a complex mosaic of differently folded regions (foldons, non-foldons, unfoldons, semi-foldons, and inducible foldons). The functionality of resulting highly dynamic conformational ensembles is fine-tuned by various post-translational modifications and alternative splicing, and such ensembles can undergo dramatic changes at interaction with their specific partners. In other words, GPCRs and G proteins exist as sets of conformational/basic, inducible/modified, and functioning proteoforms characterized by a broad spectrum of structural features and possessing various functional potentials.read more
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Life in Phases: Intra- and Inter- Molecular Phase Transitions in Protein Solutions
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Intrinsically disordered proteins play diverse roles in cell signaling
TL;DR: In this article , the authors highlight the critical role of intrinsically disordered proteins for signaling in widely diverse organisms (animals, plants, bacteria, fungi), in every category of cell signaling pathway (autocrine, juxtacrine, intracrine and paracrine) and at each stage (ligand, receptor, transducer, effector, terminator) in the cell signaling process.
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Intrinsically disordered proteins play diverse roles in cell signaling
TL;DR: In this paper , the authors highlight the critical role of intrinsically disordered proteins for signaling in widely diverse organisms (animals, plants, bacteria, fungi), in every category of cell signaling pathway (autocrine, juxtacrine, intracrine and paracrine) and at each stage (ligand, receptor, transducer, effector, terminator) in the cell signaling process.
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On the specificity of protein-protein interactions in the context of disorder.
TL;DR: In this paper, the authors discuss the differences between globular proteins and intrinsically disordered proteins (IDPs) in terms of their interactome sizes and their ability to adapt to different binding partners.
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