Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3.
Cell Discov
; 8(1): 44, 2022 May 15.
Article
em En
| MEDLINE
| ID: mdl-35570218
ABSTRACT
Chemokine receptors are a family of G-protein-coupled receptors with key roles in leukocyte migration and inflammatory responses. Here, we present cryo-electron microscopy structures of two human CC chemokine receptor-G-protein complexes CCR2 bound to its endogenous ligand CCL2, and CCR3 in the apo state. The structure of the CCL2-CCR2-G-protein complex reveals that CCL2 inserts deeply into the extracellular half of the transmembrane domain, and forms substantial interactions with the receptor through the most N-terminal glutamine. Extensive hydrophobic and polar interactions are present between both two chemokine receptors and the Gα-protein, contributing to the constitutive activity of these receptors. Notably, complemented with functional experiments, the interactions around intracellular loop 2 of the receptors are found to be conserved and play a more critical role in G-protein activation than those around intracellular loop 3. Together, our findings provide structural insights into chemokine recognition and receptor activation, shedding lights on drug design targeting chemokine receptors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cell Discov
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China