Welcome to MUG - Mutation Understanding for GPCRs

Mutation Understanding for GPCRs

G protein-coupled receptors (GPCRs) mediate several signalling pathways through a general mechanism that involves their activation, upholding a chain of events that lead to the release of molecules responsible for cytoplasmic action and further regulations. These physiological functions can be severely altered by mutations in GPCR genes. A comprehensive and detailed database - MUG (Mutations Understanding GPCRs) - was constructed, illustrating key reported mutations and their effect on receptors of the sub-family A17 of GPCRs (dopamine, serotonin, adrenergic and trace amine receptors). Mutations were also sub-classified into groups of residues known to be important for receptor signalling. Here, we provide an analysis of the type of mutations occurring overall and in the different families of the sub-family A17, as well the effects they have on receptor functionality, and their particular localization within the receptor. The residues were further analysed considering age distribution.

The results reveal a diversity of mutations in the diverse GPCRs sub-family A17 structures, drawing attention to the considerable number of mutations in conserved residues and domains. Mutated residues were enriched at the ligand binding pocket and known activating microdomains, which may lead to disruption of the receptor function. Mutating residues were enriched in hydrophobic residues. Furthermore, heterogeneous distribution of mutations in the different age groups was observed, suggesting that the number of mutations does not seem to increase with age but was rather found to be restricted to specific age groups. We expect that this interactive database helps to explore mutations, their influence and their effects familywise and receptor specific, constituting the first step in elucidating the structural and molecular interactions at the atomic level.

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