GPCR-G protein selectivity revealed by structural pharmacology.
FEBS J
; 291(13): 2784-2791, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38151714
ABSTRACT
Receptor-G protein promiscuity is frequently observed in class A G protein-coupled receptors (GPCRs). In particular, GPCRs can couple with G proteins from different families (Gαs, Gαq/11, Gαi/o, and Gα12/13) or the same family subtypes. The molecular basis underlying the selectivity/promiscuity is not fully revealed. We recently reported the structures of kappa opioid receptor (KOR) in complex with the Gi/o family subtypes [Gαi1, GαoA, Gαz, and Gustducin (Gαg)] determined by cryo-electron microscopy (cryo-EM). The structural analysis, in combination with pharmacological studies, provides insights into Gi/o subtype selectivity. Given the conserved sequence identity and activation mechanism between different G protein families, the findings within Gi/o subtypes could be likely extended to other families. Understanding the KOR-Gi/o or GPCR-G protein selectivity will facilitate the development of more precise therapeutics targeting a specific G protein subtype.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Opioid, kappa
/
Cryoelectron Microscopy
/
Receptors, G-Protein-Coupled
Limits:
Animals
/
Humans
Language:
En
Journal:
FEBS J
Journal subject:
BIOQUIMICA
Year:
2024
Document type:
Article
Affiliation country: