Analysis of role of aromatic residues in extracellular loop 2 of Prokineticin receptor 2 in ligand binding probed with genetically encoded photo-crosslinkers

2021 ◽  
pp. 183549
Author(s):  
Maria Rosaria Fullone ◽  
Roberta Lattanzi ◽  
Daniela Maftei ◽  
Maria Carmela Bonaccorsi ◽  
Rossella Miele
Keyword(s):  
Ligand Binding ◽  
Extracellular Loop ◽  
Aromatic Residues ◽  
Loop 2

scholarly journals Role of Conserved Disulfide Bridges and Aromatic Residues in Extracellular Loop 2 of Chemokine Receptor CCR8 for Chemokine and Small Molecule Binding

2016 ◽  
Vol 291 (31) ◽  
pp. 16208-16220 ◽  
Author(s):  
Line Barington ◽  
Pia C. Rummel ◽  
Michael Lückmann ◽  
Heidi Pihl ◽  
Olav Larsen ◽  
...  
Keyword(s):  
Small Molecule ◽  
Chemokine Receptor ◽  
Disulfide Bridges ◽  
Extracellular Loop ◽  
Aromatic Residues ◽  
Loop 2

scholarly journals FSH receptor-specific residues L501 and I505 in extracellular loop 2 are essential for its function

2015 ◽  
Vol 54 (3) ◽  
pp. 193-204 ◽  
Author(s):  
Antara A Banerjee ◽  
Madhavi Dupakuntla ◽  
Bhakti R Pathak ◽  
Smita D Mahale
Keyword(s):  
Amino Acids ◽  
Hek293 Cells ◽  
Fsh Receptor ◽  
Receptor Function ◽  
Extracellular Loop ◽  
Camp Production ◽  
Transfected Cells ◽  
Erk Phosphorylation ◽  
Loop 2

The extracellular loop 2 (EL2) of FSH receptor (FSHR) plays a pivotal role in various events downstream of FSH stimulation. Because swapping the six FSHR-specific residues in EL2 (chimeric EL2M) with those from LH/choriogonadotropin receptor resulted in impaired internalization of FSH–FSHR complex and low FSH-induced cAMP production, six substitution mutants of EL2 were generated to ascertain the contribution of individual amino acids to the effects shown by chimeric EL2M. Results revealed that L501F mainly and I505V to a lesser extent contribute to the diminished receptor function in chimeric EL2M. HEK293 cells stably expressing WT and chimeric EL2M FSHR were generated to track the fate of the receptors post FSH induction. The chimeric EL2M FSHR stable clone showed weak internalization and cAMP response similar to transiently transfected cells. Furthermore, reduced FSH-induced ERK phosphorylation was also observed. The interaction of activated chimeric EL2M and L501F FSHR with β-arrestins was weak compared with WT FSHR, thus explaining the impaired internalization of chimeric EL2M and corroborating the indispensable role of EL2 in receptor function.

scholarly journals Characterization of feline ASCT1 and ASCT2 as RD-114 virus receptor

2013 ◽  
Vol 94 (7) ◽  
pp. 1608-1612 ◽  
Author(s):  
Sayumi Shimode ◽  
Rie Nakaoka ◽  
Hiroko Shogen ◽  
Takayuki Miyazawa
Keyword(s):  
Endogenous Retrovirus ◽  
Amino Acid Transporters ◽  
Extracellular Loop ◽  
Virus Receptor ◽  
Metabolic Role ◽  
Virus Receptors ◽  
Sodium Dependent ◽  
Loop 2

RD-114 virus is a replication-competent feline endogenous retrovirus (ERV). RD-114 virus had been thought to be xenotropic; however, recent findings indicate that RD-114 virus is polytropic and can infect and grow efficiently in feline cells. Receptor(s) for RD-114 virus has not been identified and characterized in cats. In this study, we confirmed that two feline sodium-dependent neutral amino acid transporters (ASCTs), fASCT1 and fASCT2, function as RD-114 virus receptors. By chimeric analyses of feline and murine ASCTs, we revealed that extracellular loop 2 of both fASCT1 and fASCT2 determines the susceptibility to RD-114 virus. Further, we revealed ubiquitous expression of these genes, consistent with the general metabolic role of the ASCT molecules. Our study indicates that RD-114 virus may reinfect tissues and cells in cats, once the virus is activated. Implications of the involvement of RD-114 virus in feline oncogenesis are also discussed.

scholarly journals Dual Role of the Second Extracellular Loop of the Cannabinoid Receptor 1: Ligand Binding and Receptor Localization

2009 ◽  
Vol 76 (4) ◽  
pp. 833-842 ◽  
Author(s):  
Kwang H. Ahn ◽  
Alexander C. Bertalovitz ◽  
Dale F. Mierke ◽  
Debra A. Kendall
Keyword(s):  
Ligand Binding ◽  
Cannabinoid Receptor ◽  
Dual Role ◽  
Extracellular Loop ◽  
Cannabinoid Receptor 1 ◽  
Receptor Localization

scholarly journals Ligand-Induced and -Independent Internalization of the Chemerin Receptor GPR1

2021 ◽  
Author(s):  
Tobias F. Fischer ◽  
Anne S. Czerniak ◽  
Tina Weiß ◽  
Clara T. Schoeder ◽  
Philipp Wolf ◽  
...  
Keyword(s):  
Binding Mode ◽  
Loop Structure ◽  
Ligand Specificity ◽  
Extracellular Loop ◽  
Extracellular Loops ◽  
C Terminus ◽  
Loop 2 ◽  
G Protein Coupled ◽  
Migration Of Macrophages

Abstract 1. Tight regulation of cytokines is essential for the initiation and resolution of inflammation. Chemerin, a mediator of innate immunity, mainly acts on chemokine-like receptor 1 (CMKLR1) to induce the migration of macrophages and dendritic cells. The role of the second chemerin receptor, G protein-coupled receptor 1 (GPR1), is still unclear. Here we demonstrate that GPR1 shows ligand-induced arrestin3 recruitment and internalization. The chemerin C-terminus triggers this activation by folding into a loop structure, binding to aromatic residues in the extracellular loops of GPR1. While this overall binding mode is shared between GPR1 and CMKLR1, differences in their respective extracellular loop 2 allowed for the design of the first GPR1-selective peptide. However, our results suggest that ligand-induced arrestin recruitment is not the only mode of action of GPR1. This receptor also displays constitutive internalization and recycling, which allows GPR1 to internalize inactive peptides efficiently by an activation-independent pathway. Our results demonstrate that GPR1 takes a dual role in regulating chemerin activity: As a signaling receptor for arrestin-based signaling on one hand, and as a scavenging receptor with broader ligand specificity on the other.

Sign in / Sign up

Export Citation Format

Share Document