Understanding the molecular functions of the second extracellular loop (ECL2) of the calcitonin gene-related peptide (CGRP) receptor using a comprehensive mutagenesis approach

@article{Woolley2017UnderstandingTM,
  title={Understanding the molecular functions of the second extracellular loop (ECL2) of the calcitonin gene-related peptide (CGRP) receptor using a comprehensive mutagenesis approach},
  author={Michael. J. Woolley and John Simms and Juan Carlos Mobarec and Christopher A. Reynolds and David R Poyner and Alex C Conner},
  journal={Molecular and Cellular Endocrinology},
  year={2017},
  volume={454},
  pages={39-49}
}
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6 Citations

Photoaffinity Cross-Linking and Unnatural Amino Acid Mutagenesis Reveal Insights into Calcitonin Gene-Related Peptide Binding to the Calcitonin Receptor-like Receptor/Receptor Activity-Modifying Protein 1 (CLR/RAMP1) Complex.

TLDR
A photoaffinity cross-linker, p-azido l-phenylalanine (azF), was incorporated into CLR, chiefly in the second extracellular loop (ECL2) using genetic code expansion and unnatural amino acid mutagenesis to ensure efficient photolysis of azF residues near the transmembrane bundle of the receptor.

Photoa ffi nity Cross-Linking and Unnatural Amino Acid Mutagenesis Reveal Insights into Calcitonin Gene-Related Peptide Binding to the Calcitonin Receptor-like Receptor / Receptor Activity-Modifying Protein 1 ( CLR / RAMP 1 ) Complex

TLDR
A photoaffinity cross-linker, p-azido Lphenylalanine (azF), was incorporated into CLR, chiefly in the second extracellular loop (ECL2) using genetic code expansion and unnatural amino acid mutagenesis to ensure efficient photolysis of azF residues near the transmembrane bundle of the receptor.

Structure and dynamics of the CGRP receptor in apo and peptide-bound forms

TLDR
The structures of an unmodified calcitonin gene–related peptide receptor, which is implicated in migraines, are determined, which show that initial binding of the peptide causes only minor conformational changes of the GPCR, but dynamically causes changes at the intracellular side that facilitate G protein binding and activation.

Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor

TLDR
Structural insight is provided into the regulation of G-protein-coupled receptors by receptor activity modifying protein 1 and molecular dynamics simulations indicate that RAMP1 provides stability to the receptor complex, particularly in the positioning of the extracellular domain of CLR.

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Differential GLP-1R binding and activation by peptide and non-peptide agonists

TLDR
High resolution cryo-EM structures reveal the binding sites for PF-06882961 and GLP-1 substantially overlap, whereas OWL-833 adopts a unique binding mode with a more open receptor conformation at the extracellular face, which will facilitate rational structure-based discovery of non-peptide agonists targeting class B GPCRs.

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