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 computational framework - 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). We explored the type of mutations occurring overall and in the different families of the sub-family A17, as well their localization within the receptor, and potential effects on receptor functionality. The mutated residues were further analysed considering age distribution.

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

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