Role of post-translational modifications on structure, function and pharmacology of class C G protein-coupled receptors

AbstractInflammation has been well recognized as one of the main drivers of atherosclerosis development and therefore cardiovascular diseases (CVDs). It has been shown that several chemokines, small 8 to 12 kDa cytokines with chemotactic properties, play a crucial role in the pathophysiology of atherosclerosis. Chemokines classically mediate their effects by binding to G-protein-coupled receptors called chemokine receptors. In addition, chemokines can also bind to atypical chemokine receptors (ACKRs). ACKRs fail to induce G-protein-dependent signalling pathways and thus subsequent cellular response, but instead are able to internalize, scavenge or transport chemokines. In this review, we will give an overview of the current knowledge about the involvement of ACKR1–4 in CVDs and especially in atherosclerosis development. In the recent years, several studies have highlighted the importance of ACKRs in CVDs, although there are still several controversies and unexplored aspects that have to be further elucidated. A better understanding of the precise role of these atypical receptors may pave the way towards novel and improved therapeutic strategies.

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Update 1 of: Computational Modeling Approaches to Structure–Function Analysis of G Protein-Coupled Receptors

Chemical Reviews ◽

10.1021/cr100437t ◽

2011 ◽

Vol 111 (12) ◽

pp. PR438-PR535 ◽

Cited By ~ 52

Author(s):

Francesca Fanelli ◽

Pier G. De Benedetti

Keyword(s):

Computational Modeling ◽

Structure Function ◽

G Protein ◽

Function Analysis ◽

G Protein Coupled Receptors ◽

Modeling Approaches ◽

G Protein Coupled

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The Role of MC1R in Speciation & Phylogeny

The American Biology Teacher ◽

10.1525/abt.2013.75.9.8 ◽

2013 ◽

Vol 75 (9) ◽

pp. 670-676 ◽

Cited By ~ 1

Author(s):

Susan Offner

Keyword(s):

G Protein ◽

Point Mutation ◽

Solomon Island ◽

G Protein Coupled Receptors ◽

Ancestral Population ◽

Mc1r Gene ◽

The Many ◽

Evolutionary Consequences ◽

G Protein Coupled

A point mutation in the MC1R gene, a G-protein-coupled receptor, has been found that could have led to the formation of two subspecies of Solomon Island flycatcher from a single ancestral population. I discuss the many roles that G-protein-coupled receptors play in vertebrate physiology and how one particular point mutation can have enormous evolutionary consequences.

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Label noise in subtype discrimination of class C G protein-coupled receptors: A systematic approach to the analysis of classification errors

BMC Bioinformatics ◽

10.1186/s12859-015-0731-9 ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 7

Author(s):

Caroline König ◽

Martha I Cárdenas ◽

Jesús Giraldo ◽

René Alquézar ◽

Alfredo Vellido

Keyword(s):

G Protein ◽

Systematic Approach ◽

G Protein Coupled Receptors ◽

Label Noise ◽

Classification Errors ◽

Class C ◽

G Protein Coupled

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New thoughts on the role of the βγ subunit in G protein signal transduction

Biochemistry and Cell Biology ◽

10.1139/o00-075 ◽

2000 ◽

Vol 78 (5) ◽

pp. 537-550 ◽

Cited By ~ 1

Author(s):

Barbara Vanderbeld ◽

Gregory M Kelly

Keyword(s):

Signal Transduction ◽

G Protein ◽

G Proteins ◽

G Protein Coupled Receptors ◽

Limited Information ◽

Α Subunit ◽

Downstream Effectors ◽

Receptor Signal ◽

G Protein Coupled

Heterotrimeric G proteins are involved in numerous biological processes, where they mediate signal transduction from agonist-bound G-protein-coupled receptors to a variety of intracellular effector molecules and ion channels. G proteins consist of two signaling moieties: a GTP-bound α subunit and a βγ heterodimer. The βγ dimer, recently credited as a significant modulator of G-protein-mediated cellular responses, is postulated to be a major determinant of signaling fidelity between G-protein-coupled receptors and downstream effectors. In this review we have focused on the role of βγ signaling and have included examples to demonstrate the heterogeneity in the heterodimer composition and its implications in signaling fidelity. We also present an overview of some of the effectors regulated by βγ and draw attention to the fact that, although G proteins and their associated receptors play an instrumental role in development, there is rather limited information on βγ signaling in embryogenesis.Key words: G protein, βγ subunit, G-protein-coupled receptor, signal transduction, adenylyl cyclase.

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