scholarly journals A short amino acid sequence containing tyrosine in the N-terminal region of G protein-coupled receptors is critical for their potential use as co-receptors for human and simian immunodeficiency viruses

2008 ◽  
Vol 89 (12) ◽  
pp. 3126-3136 ◽  
Author(s):  
Nobuaki Shimizu ◽  
Atsushi Tanaka ◽  
Atsushi Oue ◽  
Takahisa Mori ◽  
Chatchawann Apichartpiyakul ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Terminal Region ◽  
Receptor Activity ◽  
Formyl Peptide Receptor ◽  
Immunodeficiency Virus ◽  
Formyl Peptide ◽  
Short Amino Acid Sequence ◽  
G Protein Coupled ◽  
Hiv 1

Various G protein-coupled receptors (GPCRs) have the potential to work as co-receptors for human and simian immunodeficiency virus (HIV/SIV). HIV/SIV co-receptors have several tyrosines in their extracellular N-terminal region (NTR) as a common feature. However, the domain structure of the NTR that is critical for GPCRs to have co-receptor activity has not been identified. Comparative studies of different HIV/SIV co-receptors are an effective way to clarify the domain. These studies have been carried out only for the major co-receptors, CCR5 and CXCR4. A chemokine receptor, D6, has been shown to mediate infection of astrocytes with HIV-1. Recently, it was also found that an orphan GPCR, GPR1, and a formyl peptide receptor, FPRL1, work as potent HIV/SIV co-receptors in addition to CCR5 and CXCR4. To elucidate more about the domain of the NTR critical for HIV/SIV co-receptor activity, this study analysed the effects of mutations in the NTR on the co-receptor activity of D6, FPRL1 and GPR1 in addition to CCR5. The results identified a number of tyrosines that are indispensable for the activity of these co-receptors. The number and positions of those tyrosines varied among co-receptors and among HIV-1 strains. Moreover, it was found that a small domain of a few amino acids containing a tyrosine is critical for the co-receptor activity of GPR1. These findings will be useful in elucidating the mechanism that allows GPCRs to have the potential to act as HIV/SIV co-receptors.

scholarly journals G-protein–coupled formyl peptide receptors play a dual role in neutrophil chemotaxis and bacterial phagocytosis

2019 ◽  
Vol 30 (3) ◽  
pp. 346-356 ◽  
Author(s):  
Xi Wen ◽  
Xuehua Xu ◽  
Wenxiang Sun ◽  
Keqiang Chen ◽  
Miao Pan ◽  
...  
Keyword(s):  
G Protein ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Actin Polymerization ◽  
G Protein Coupled Receptors ◽  
Peptide Receptors ◽  
Tyrosine Kinase Signaling ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
G Protein Coupled

A dogma of innate immunity is that neutrophils use G-protein–coupled receptors (GPCRs) for chemoattractant to chase bacteria through chemotaxis and then use phagocytic receptors coupled with tyrosine kinases to destroy opsonized bacteria via phagocytosis. Our current work showed that G-protein–coupled formyl peptide receptors (FPRs) directly mediate neutrophil phagocytosis. Mouse neutrophils lacking formyl peptide receptors (Fpr1/2–/–) are defective in the phagocytosis of Escherichia coli and the chemoattractant N-formyl-Met-Leu-Phe (fMLP)-coated beads. fMLP immobilized onto the surface of a bead interacts with FPRs, which trigger a Ca2+response and induce actin polymerization to form a phagocytic cup for engulfment of the bead. This chemoattractant GPCR/Gi signaling works independently of phagocytic receptor/tyrosine kinase signaling to promote phagocytosis. Thus, in addition to phagocytic receptor-mediated phagocytosis, neutrophils also utilize the chemoattractant GPCR/Gi signaling to mediate phagocytosis to fight against invading bacteria.

G-protein-coupled receptor allosterism: the promise and the problem(s)

2004 ◽  
Vol 32 (5) ◽  
pp. 873-877 ◽  
Author(s):  
A. Christopoulos ◽  
L.T. May ◽  
V.A. Avlani ◽  
P.M. Sexton
Keyword(s):  
G Protein ◽  
Binding Sites ◽  
G Protein Coupled Receptors ◽  
Receptor Activity ◽  
Screening Methods ◽  
Receptor Subtype ◽  
Allosteric Modulators ◽  
Physiological Regulation ◽  
Subtype Selectivity ◽  
G Protein Coupled

Allosteric modulators of G-protein-coupled receptors interact with binding sites that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Allosteric ligands offer a number of advantages over orthosteric drugs, including the potential for greater receptor subtype selectivity and a more ‘physiological’ regulation of receptor activity. However, the manifestations of allosterism at G-protein-coupled receptors are quite varied, and significant challenges remain for the optimization of screening methods to ensure the routine detection and validation of allosteric ligands.

scholarly journals Experimental Evidence for Lack of Homodimerization of the G Protein-Coupled HumanN-Formyl Peptide Receptor

2003 ◽  
Vol 171 (6) ◽  
pp. 3187-3193 ◽  
Author(s):  
Jeannie M. Gripentrog ◽  
Katrin P. Kantele ◽  
Algirdas J. Jesaitis ◽  
Heini M. Miettinen
Keyword(s):  
Experimental Evidence ◽  
G Protein ◽  
Formyl Peptide Receptor ◽  
Peptide Receptor ◽  
Formyl Peptide ◽  
G Protein Coupled

scholarly journals G protein subtype–specific signaling bias in a series of CCR5 chemokine analogs

2018 ◽  
Vol 11 (552) ◽  
pp. eaao6152 ◽  
Author(s):  
Emily Lorenzen ◽  
Emilie Ceraudo ◽  
Yamina A. Berchiche ◽  
Carlos A. Rico ◽  
Alexandre Fürstenberg ◽  
...  
Keyword(s):  
G Protein ◽  
Chemokine Receptor ◽  
General Feature ◽  
G Protein Coupled Receptors ◽  
Second Messenger Pathways ◽  
Chemokine Receptor 4 ◽  
Ligand Bias ◽  
G Protein Coupled ◽  
Hiv 1 ◽  
The Ideal

Chemokines and some chemical analogs of chemokines prevent cellular HIV-1 entry when bound to the HIV-1 coreceptors C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor 4 (CXCR4), which are G protein–coupled receptors (GPCRs). The ideal HIV-1 entry blocker targeting the coreceptors would display ligand bias and avoid activating G protein–mediated pathways that lead to inflammation. We compared CCR5-dependent activation of second messenger pathways in a single cell line. We studied two endogenous chemokines [RANTES (also known as CCL5) and MIP-1α (also known as CCL3)] and four chemokine analogs of RANTES (5P12-, 5P14-, 6P4-, and PSC-RANTES). We found that CCR5 signaled through both Gi/o and Gq/11. IP1 accumulation and Ca2+ flux arose from Gq/11 activation, rather than from Gβγ subunit release after Gi/o activation as had been previously proposed. The 6P4- and PSC-RANTES analogs were superagonists for Gq/11 activation, whereas the 5P12- and 5P14-RANTES analogs displayed a signaling bias for Gi/o. These results demonstrate that RANTES analogs elicit G protein subtype–specific signaling bias and can cause CCR5 to couple preferentially to Gq/11 rather than to Gi/o signaling pathways. We propose that G protein subtype–specific signaling bias may be a general feature of GPCRs that can couple to more than one G protein family.

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