scholarly journals Structural basis of G protein–coupled receptor–G protein interactions

2010 ◽  
Vol 6 (7) ◽  
pp. 541-548 ◽  
Author(s):  
Jianxin Hu ◽  
Yan Wang ◽  
Xiaohong Zhang ◽  
John R Lloyd ◽  
Jian Hua Li ◽  
...  
Keyword(s):  
G Protein ◽  
Protein Interactions ◽  
Structural Basis ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Structural Characterization of Receptor–Receptor Interactions in the Allosteric Modulation of G Protein-Coupled Receptor (GPCR) Dimers

2021 ◽  
Vol 22 (6) ◽  
pp. 3241
Author(s):  
Raudah Lazim ◽  
Donghyuk Suh ◽  
Jai Woo Lee ◽  
Thi Ngoc Lan Vu ◽  
Sanghee Yoon ◽  
...  
Keyword(s):  
G Protein ◽  
Protein Interactions ◽  
Metabotropic Glutamate Receptor ◽  
Three Dimensional ◽  
Allosteric Modulation ◽  
Experimental Investigations ◽  
G Protein Coupled Receptor ◽  
Metabotropic Glutamate ◽  
Gpcr Activation ◽  
G Protein Coupled

G protein-coupled receptor (GPCR) oligomerization, while contentious, continues to attract the attention of researchers. Numerous experimental investigations have validated the presence of GPCR dimers, and the relevance of dimerization in the effectuation of physiological functions intensifies the attractiveness of this concept as a potential therapeutic target. GPCRs, as a single entity, have been the main source of scrutiny for drug design objectives for multiple diseases such as cancer, inflammation, cardiac, and respiratory diseases. The existence of dimers broadens the research scope of GPCR functions, revealing new signaling pathways that can be targeted for disease pathogenesis that have not previously been reported when GPCRs were only viewed in their monomeric form. This review will highlight several aspects of GPCR dimerization, which include a summary of the structural elucidation of the allosteric modulation of class C GPCR activation offered through recent solutions to the three-dimensional, full-length structures of metabotropic glutamate receptor and γ-aminobutyric acid B receptor as well as the role of dimerization in the modification of GPCR function and allostery. With the growing influence of computational methods in the study of GPCRs, we will also be reviewing recent computational tools that have been utilized to map protein–protein interactions (PPI).

Interprotein interactions are responsible for the confined diffusion of a G-protein-coupled receptor at the cell surface

2003 ◽  
Vol 31 (5) ◽  
pp. 1001-1005 ◽  
Author(s):  
F. Daumas ◽  
N. Destainville ◽  
C. Millot ◽  
A. Lopez ◽  
D. Dean ◽  
...  
Keyword(s):  
G Protein ◽  
Protein Interactions ◽  
Domain Size ◽  
Single Particle Tracking ◽  
G Protein Coupled Receptor ◽  
Short Term ◽  
Detailed Statistical Analysis ◽  
G Protein Coupled ◽  
Dynamic Organization

The monitoring of the movements of membrane proteins (or lipids) by single-particle tracking enables one to obtain reliable insights into the complex dynamic organization of the plasma membrane constituents. Using this technique, we investigated the diffusional behaviour of a G-protein-coupled receptor. The trajectories of the receptors revealed a diffusion mode combining a short-term rapid confined diffusion with a long-term slow diffusion. A detailed statistical analysis shows that the receptors have a diffusion confined to a domain which itself diffuses, the confinement being due to long-range attractive inter-protein interactions. The existing models of the dynamic organization of the cell membrane cannot explain our results. We propose a theoretical Brownian model of interacting proteins that is consistent with the experimental observations and accounts for the variations found as a function of the domain size of the short-term and long-term diffusion coefficients.

Structural basis of G protein-coupled receptor function

1999 ◽  
Vol 151 (1-2) ◽  
pp. 181-193 ◽  
Author(s):  
Torsten Schöneberg ◽  
Günter Schultz ◽  
Thomas Gudermann
Keyword(s):  
G Protein ◽  
Structural Basis ◽  
Receptor Function ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome

2017 ◽  
Vol 114 (51) ◽  
pp. 13453-13458 ◽  
Author(s):  
John J. Skinner ◽  
Sheng Wang ◽  
Jiyoung Lee ◽  
Colin Ong ◽  
Ruth Sommese ◽  
...  
Keyword(s):  
G Protein ◽  
Protein Interactions ◽  
Salt Bridge ◽  
G Protein Coupled Receptor ◽  
Inhibitory Protein ◽  
Raf Kinase ◽  
Protein Interfaces ◽  
Partial Unfolding ◽  
Direct Recognition ◽  
G Protein Coupled

Phosphorylation is a major regulator of protein interactions; however, the mechanisms by which regulation occurs are not well understood. Here we identify a salt-bridge competition or “theft” mechanism that enables a phospho-triggered swap of protein partners by Raf Kinase Inhibitory Protein (RKIP). RKIP transitions from inhibiting Raf-1 to inhibiting G-protein–coupled receptor kinase 2 upon phosphorylation, thereby bridging MAP kinase and G-Protein–Coupled Receptor signaling. NMR and crystallography indicate that a phosphoserine, but not a phosphomimetic, competes for a lysine from a preexisting salt bridge, initiating a partial unfolding event and promoting new protein interactions. Structural elements underlying the theft occurred early in evolution and are found in 10% of homo-oligomers and 30% of hetero-oligomers including Bax, Troponin C, and Early Endosome Antigen 1. In contrast to a direct recognition of phosphorylated residues by binding partners, the salt-bridge theft mechanism represents a facile strategy for promoting or disrupting protein interactions using solvent-accessible residues, and it can provide additional specificity at protein interfaces through local unfolding or conformational change.

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