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): 3877-3880, 2017 08 01.
Article
en En
| MEDLINE
| ID: mdl-28691801
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Transducción de Señal
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Modelos Moleculares
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Péptido Relacionado con Gen de Calcitonina
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Receptores de Péptido Relacionado con el Gen de Calcitonina
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Proteína 1 Modificadora de la Actividad de Receptores
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Proteína Similar al Receptor de Calcitonina
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Mióticos
Idioma:
En
Revista:
Biochemistry
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido