scholarly journals Specificity of Porcine Calcitonin Receptor and Calcitonin Receptor-like Receptor in the Presence of Receptor-Activity-Modifying Proteins

2003 ◽  
Vol 26 (Suppl) ◽  
pp. S15-S23 ◽  
Author(s):  
Katsuro KIKUMOTO ◽  
Takeshi KATAFUCHI ◽  
Naoto MINAMINO
Keyword(s):  
Receptor Activity ◽  
Calcitonin Receptor ◽  
Receptor Activity Modifying Proteins

Receptor Activity Modifying Proteins Have Limited Effects on the Class B G Protein-Coupled Receptor Calcitonin Receptor-Like Receptor Stalk

Biochemistry ◽  
2018 ◽  
Vol 57 (8) ◽  
pp. 1410-1422 ◽  
Author(s):  
Michael L. Garelja ◽  
Christina A. Walker ◽  
Andrew Siow ◽  
Sung H. Yang ◽  
Paul W.R. Harris ◽  
...  
Keyword(s):  
G Protein ◽  
Receptor Activity ◽  
Calcitonin Receptor ◽  
G Protein Coupled Receptor ◽  
Class B ◽  
Receptor Activity Modifying Proteins ◽  
G Protein Coupled

scholarly journals An allosteric role for receptor activity-modifying proteins in defining GPCR pharmacology

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Joseph J Gingell ◽  
John Simms ◽  
James Barwell ◽  
David R Poyner ◽  
Harriet A Watkins ◽  
...  
Keyword(s):  
G Protein ◽  
Protein Interaction ◽  
G Protein Coupled Receptors ◽  
Receptor Activity ◽  
Calcitonin Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Receptor Activity Modifying Proteins ◽  
G Protein Coupled ◽  
Insight Into

Abstract G protein-coupled receptors are allosteric proteins that control transmission of external signals to regulate cellular response. Although agonist binding promotes canonical G protein signalling transmitted through conformational changes, G protein-coupled receptors also interact with other proteins. These include other G protein-coupled receptors, other receptors and channels, regulatory proteins and receptor-modifying proteins, notably receptor activity-modifying proteins (RAMPs). RAMPs have at least 11 G protein-coupled receptor partners, including many class B G protein-coupled receptors. Prototypic is the calcitonin receptor, with altered ligand specificity when co-expressed with RAMPs. To gain molecular insight into the consequences of this protein–protein interaction, we combined molecular modelling with mutagenesis of the calcitonin receptor extracellular domain, assessed in ligand binding and functional assays. Although some calcitonin receptor residues are universally important for peptide interactions (calcitonin, amylin and calcitonin gene-related peptide) in calcitonin receptor alone or with receptor activity-modifying protein, others have RAMP-dependent effects, whereby mutations decreased amylin/calcitonin gene-related peptide potency substantially only when RAMP was present. Remarkably, the key residues were completely conserved between calcitonin receptor and AMY receptors, and between subtypes of AMY receptor that have different ligand preferences. Mutations at the interface between calcitonin receptor and RAMP affected ligand pharmacology in a RAMP-dependent manner, suggesting that RAMP may allosterically influence the calcitonin receptor conformation. Supporting this, molecular dynamics simulations suggested that the calcitonin receptor extracellular N-terminal domain is more flexible in the presence of receptor activity-modifying protein 1. Thus, RAMPs may act in an allosteric manner to generate a spectrum of unique calcitonin receptor conformational states, explaining the pharmacological preferences of calcitonin receptor-RAMP complexes. This provides novel insight into our understanding of G protein-coupled receptor-protein interaction that is likely broadly applicable for this receptor class.

scholarly journals Visualization of the Calcitonin Receptor-like Receptor and Its Receptor Activity-modifying Proteins during Internalization and Recycling

2000 ◽  
Vol 275 (38) ◽  
pp. 29602-29609 ◽  
Author(s):  
Kenji Kuwasako ◽  
Yoshiyuki Shimekake ◽  
Michitaka Masuda ◽  
Koichiro Nakahara ◽  
Tetsuya Yoshida ◽  
...  
Keyword(s):  
Receptor Activity ◽  
Calcitonin Receptor ◽  
Receptor Activity Modifying Proteins
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