Woolley, Michael J., Simms, John, Uddin, Sifat, Poyner, David R. and Conner, Alex C.
(2017).
Relative antagonism of mutants of the CGRP receptor extracellular loop 2 domain (ECL2) using a truncated competitive antagonist (CGRP8-37):evidence for the dual involvement of ECL2 in the two-domain binding model.
Biochemistry, 56
(30),
pp. 3877-3880.
Abstract
The second extracellular loop (ECL2) of the G protein-coupled receptor (GPCR) family is important for ligand interaction and drug discovery. ECL2 of the family B cardioprotective calcitonin gene-related peptide (CGRP) receptor is required for cell signaling. Family B GPCR ligands have two regions; the N-terminus mediates receptor activation, and the remainder confers high-affinity binding. Comparing antagonism of CGRP8-37 at a number of point mutations of ECL2 of the CGRP receptor, we show that the ECL2 potentially facilitates interaction with up to the 18 N-terminal residues of CGRP. This has implications for understanding family B GPCR activation and for drug design at the CGRP receptor.
Publication DOI: | https://doi.org/10.1021/acs.biochem.7b00077 |
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Divisions: | Life & Health Sciences > Biosciences Life & Health Sciences > Pharmacy Life & Health Sciences |
Additional Information: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.biochem.7b00077 Funding: BHF (PG/12/59/29795); BBSRC (BB/M007529/1). |
Uncontrolled Keywords: | Biochemistry |
Full Text Link: | |
Related URLs: |
http://www.scopus.com/inward/record.url?scp=85026660660&partnerID=8YFLogxK
(Scopus URL) |
Published Date: | 2017-08 |
Authors: |
Woolley, Michael J.
Simms, John Uddin, Sifat Poyner, David R. ( ![]() Conner, Alex C. |