MUG: A mutation overview of GPCR subfamily A17 receptors
G protein-coupled receptors (GPCRs) mediate several signaling 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 regulation. These physiological functions can be severel...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022005918 |
| _version_ | 1797384163012116480 |
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| author | Ana B. Caniceiro Beatriz Bueschbell Carlos A.V. Barreto António J. Preto Irina S. Moreira |
| author_facet | Ana B. Caniceiro Beatriz Bueschbell Carlos A.V. Barreto António J. Preto Irina S. Moreira |
| author_sort | Ana B. Caniceiro |
| collection | DOAJ |
| description | G protein-coupled receptors (GPCRs) mediate several signaling 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 regulation. These physiological functions can be severely altered by mutations in GPCR genes. GPCRs subfamily A17 (dopamine, serotonin, adrenergic and trace amine receptors) are directly related with neurodegenerative diseases, and as such it is crucial to explore known mutations on these systems and their impact in structure and function. A comprehensive and detailed computational framework - MUG (Mutations Understanding GPCRs) - was constructed, illustrating key reported mutations and their effect on receptors of the subfamily A17 of GPCRs. We explored the type of mutations occurring overall and in the different families of subfamily A17, as well their localization within the receptor and potential effects on receptor functionality. The mutated residues were further analyzed considering their pathogenicity. The results reveal a high diversity of mutations in the GPCR subfamily 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 receptor function. MUG as an interactive web application is available for the management and visualization of this dataset. We expect that this interactive database helps the exploration of GPCR mutations, their influence, and their familywise and receptor-specific effects, constituting the first step in elucidating their structures and molecules at the atomic level. |
| first_indexed | 2024-03-08T21:31:30Z |
| format | Article |
| id | doaj.art-aeff22ed4fea4ad29625b37b5c201ab4 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:31:30Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-aeff22ed4fea4ad29625b37b5c201ab42023-12-21T07:30:35ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-0121586600MUG: A mutation overview of GPCR subfamily A17 receptorsAna B. Caniceiro0Beatriz Bueschbell1Carlos A.V. Barreto2António J. Preto3Irina S. Moreira4CNC - Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; PhD in Biosciences, Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, PortugalCNC - Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão, 3030-789 Coimbra, PortugalCNC - Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão, 3030-789 Coimbra, PortugalCNC - Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão, 3030-789 Coimbra, PortugalCNC - Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal; Corresponding author at: Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal.G protein-coupled receptors (GPCRs) mediate several signaling 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 regulation. These physiological functions can be severely altered by mutations in GPCR genes. GPCRs subfamily A17 (dopamine, serotonin, adrenergic and trace amine receptors) are directly related with neurodegenerative diseases, and as such it is crucial to explore known mutations on these systems and their impact in structure and function. A comprehensive and detailed computational framework - MUG (Mutations Understanding GPCRs) - was constructed, illustrating key reported mutations and their effect on receptors of the subfamily A17 of GPCRs. We explored the type of mutations occurring overall and in the different families of subfamily A17, as well their localization within the receptor and potential effects on receptor functionality. The mutated residues were further analyzed considering their pathogenicity. The results reveal a high diversity of mutations in the GPCR subfamily 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 receptor function. MUG as an interactive web application is available for the management and visualization of this dataset. We expect that this interactive database helps the exploration of GPCR mutations, their influence, and their familywise and receptor-specific effects, constituting the first step in elucidating their structures and molecules at the atomic level.http://www.sciencedirect.com/science/article/pii/S2001037022005918G protein-coupled receptorsGPCR subfamily A17Natural variantsDatabaseNeurodegenerative diseases |
| spellingShingle | Ana B. Caniceiro Beatriz Bueschbell Carlos A.V. Barreto António J. Preto Irina S. Moreira MUG: A mutation overview of GPCR subfamily A17 receptors Computational and Structural Biotechnology Journal G protein-coupled receptors GPCR subfamily A17 Natural variants Database Neurodegenerative diseases |
| title | MUG: A mutation overview of GPCR subfamily A17 receptors |
| title_full | MUG: A mutation overview of GPCR subfamily A17 receptors |
| title_fullStr | MUG: A mutation overview of GPCR subfamily A17 receptors |
| title_full_unstemmed | MUG: A mutation overview of GPCR subfamily A17 receptors |
| title_short | MUG: A mutation overview of GPCR subfamily A17 receptors |
| title_sort | mug a mutation overview of gpcr subfamily a17 receptors |
| topic | G protein-coupled receptors GPCR subfamily A17 Natural variants Database Neurodegenerative diseases |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022005918 |
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