Molecular signatures of G-protein-coupled receptors

@article{Venkatakrishnan2013MolecularSO,
  title={Molecular signatures of G-protein-coupled receptors},
  author={A. J. Venkatakrishnan and Xavier Deup{\'i} and Guillaume Lebon and Christopher G. Tate and Gebhard F. X. Schertler and M. Madan Babu},
  journal={Nature},
  year={2013},
  volume={494},
  pages={185-194}
}
G-protein-coupled receptors (GPCRs) are physiologically important membrane proteins that sense signalling molecules such as hormones and neurotransmitters, and are the targets of several prescribed drugs. Recent exciting developments are providing unprecedented insights into the structure and function of several medically important GPCRs. Here, through a systematic analysis of high-resolution GPCR structures, we uncover a conserved network of non-covalent contacts that defines the GPCR fold… Expand
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References

SHOWING 1-10 OF 121 REFERENCES
The structure and function of G-protein-coupled receptors
G-protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for aExpand
Diversity and modularity of G protein-coupled receptor structures.
TLDR
Common structural features are reviewed, the scope of structural diversity of GPCRs at different levels of homology is outlined, and a distinct modularity is now being observed between the extracellular (ligand-binding) and intracellular (signaling) regions. Expand
Ligand-specific regulation of the extracellular surface of a G protein coupled receptor
TLDR
NMR spectroscopy is used to demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Expand
Conserved activation pathways in G-protein-coupled receptors.
TLDR
The structure of light-activated rhodopin with all the features of the active metarhodopsin-II is determined, which represents so far the most native-like model of an active GPCR and constitutes a unique structural framework on which to understand the conserved aspects of the activation mechanism of GPCRs. Expand
Agonist-bound structures of G protein-coupled receptors.
TLDR
The structure of the β(2)-adrenoceptor coupled to a heterotrimeric G protein showed how the opening of a cleft in the cytoplasmic face of the receptor as a consequence of agonist binding results in G protein coupling and activation of the G protein. Expand
Domain coupling in GPCRs: the engine for induced conformational changes.
TLDR
Evidence is provided for the emerging paradigm of domain coupling facilitated by intrinsic disorder of the ligand-free state in GPCRs that provides a novel mechanistic basis for rational drug development, small molecule antagonism and GPCR regulation by classical as well as nonclassical modes. Expand
Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions
TLDR
The high-resolution structure of a stabilized version of the human A2Aadenosine receptor (A2AAR) reveals the position of about 60 internal waters, which suggests an almost continuous channel in the GPCR and can explain the allosteric effects of Na+ on ligand binding and how cholesterol may contribute to G PCR stabilization. Expand
Structure and Function of an Irreversible Agonist-β2 Adrenoceptor complex
TLDR
A covalent agonist-bound β2AR–T4L fusion protein is designed that can be covalently tethered to a specific site on the receptor through a disulphide bond, and is capable of activating a heterotrimeric G protein. Expand
Structural insights into biased G protein-coupled receptor signaling revealed by fluorescence spectroscopy
TLDR
This study provides unique insights into the structural mechanisms of GPCR activation by biased ligands that may be relevant to the design of pathway-biased drugs and develops fluorescence-based assays to investigate the structural basis of biased signaling for the V2R. Expand
A G protein-coupled receptor at work: the rhodopsin model.
TLDR
G protein-coupled receptors are ubiquitous signal transducers in cell membranes, as well as important drug targets, and their activation intermediates can now be interpreted as the stepwise engagement of protein domains. Expand
...
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2
3
4
5
...