Extracellular loop 2 in the FSH receptor is crucial for ligand mediated receptor activation

2012 ◽  
Vol 362 (1-2) ◽  
pp. 60-68 ◽  
Author(s):  
Madhavi Dupakuntla ◽  
Bhakti Pathak ◽  
Binita Sur Roy ◽  
Smita D. Mahale
Keyword(s):  
Receptor Activation ◽  
Fsh Receptor ◽  
Extracellular Loop ◽  
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 Cryo-EM structure of the human histamine H1 receptor/Gq complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruixue Xia ◽  
Na Wang ◽  
Zhenmei Xu ◽  
Yang Lu ◽  
Jing Song ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Binding Pocket ◽  
Receptor Activation ◽  
Intracellular Loop ◽  
Cryo Electron Microscopy ◽  
Allergy Treatment ◽  
Domain 3 ◽  
Extracellular Side ◽  
Key Residues ◽  
Loop 2

AbstractHistamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human H1R in complex with a Gq protein in an active conformation via a NanoBiT tethering strategy. The structure reveals that histamine activates receptor via interacting with the key residues of both transmembrane domain 3 (TM3) and TM6 to squash the binding pocket on the extracellular side and to open the cavity on the intracellular side for Gq engagement in a model of “squash to activate and expand to deactivate”. The structure also reveals features for Gq coupling, including the interaction between intracellular loop 2 (ICL2) and the αN-β junction of Gq/11 protein. The detailed analysis of our structure will provide a framework for understanding G-protein coupling selectivity and clues for designing novel antihistamines.

A2A and A2B adenosine receptors: The extracellular loop 2 determines high (A2A) or low affinity (A2B) for adenosine

2020 ◽  
Vol 172 ◽  
pp. 113718 ◽  
Author(s):  
Elisabetta De Filippo ◽  
Sonja Hinz ◽  
Veronica Pellizzari ◽  
Giuseppe Deganutti ◽  
Ali El-Tayeb ◽  
...  
Keyword(s):  
Adenosine Receptors ◽  
Extracellular Loop ◽  
Loop 2

scholarly journals Rearrangement of the Extracellular Domain/Extracellular Loop 1 Interface Is Critical for Thyrotropin Receptor Activation

2016 ◽  
Vol 291 (27) ◽  
pp. 14095-14108 ◽  
Author(s):  
Joerg Schaarschmidt ◽  
Marcus B. M. Nagel ◽  
Sandra Huth ◽  
Holger Jaeschke ◽  
Rocco Moretti ◽  
...  
Keyword(s):  
Extracellular Domain ◽  
Receptor Activation ◽  
Thyrotropin Receptor ◽  
Extracellular Loop

scholarly journals Second Extracellular Loop of Human Glucagon-like Peptide-1 Receptor (GLP-1R) Has a Critical Role in GLP-1 Peptide Binding and Receptor Activation

2011 ◽  
Vol 287 (6) ◽  
pp. 3642-3658 ◽  
Author(s):  
Cassandra Koole ◽  
Denise Wootten ◽  
John Simms ◽  
Laurence J. Miller ◽  
Arthur Christopoulos ◽  
...  
Keyword(s):  
Critical Role ◽  
Peptide Binding ◽  
Receptor Activation ◽  
Extracellular Loop ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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