Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR
Mutations in the chloride channel CFTR that impair plasma membrane insertion and ion transport are the cause of cystic fibrosis. Here, the authors identify a macrocycle that stabilizes the interaction of mutant CFTR with the chaperone-like protein 14-3-3 and rescues its biological function.
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-06-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-31206-6 |
| _version_ | 1811333895037124608 |
|---|---|
| author | Loes M. Stevers Madita Wolter Graeme W. Carlile Dwight Macdonald Luc Richard Frank Gielkens John W. Hanrahan David Y. Thomas Sai Kumar Chakka Mark L. Peterson Helmut Thomas Luc Brunsveld Christian Ottmann |
| author_facet | Loes M. Stevers Madita Wolter Graeme W. Carlile Dwight Macdonald Luc Richard Frank Gielkens John W. Hanrahan David Y. Thomas Sai Kumar Chakka Mark L. Peterson Helmut Thomas Luc Brunsveld Christian Ottmann |
| author_sort | Loes M. Stevers |
| collection | DOAJ |
| description | Mutations in the chloride channel CFTR that impair plasma membrane insertion and ion transport are the cause of cystic fibrosis. Here, the authors identify a macrocycle that stabilizes the interaction of mutant CFTR with the chaperone-like protein 14-3-3 and rescues its biological function. |
| first_indexed | 2024-04-13T16:59:41Z |
| format | Article |
| id | doaj.art-92fd952667d14a1ba9705d63a6a37de1 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-13T16:59:41Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-92fd952667d14a1ba9705d63a6a37de12022-12-22T02:38:43ZengNature PortfolioNature Communications2041-17232022-06-011311910.1038/s41467-022-31206-6Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTRLoes M. Stevers0Madita Wolter1Graeme W. Carlile2Dwight Macdonald3Luc Richard4Frank Gielkens5John W. Hanrahan6David Y. Thomas7Sai Kumar Chakka8Mark L. Peterson9Helmut Thomas10Luc Brunsveld11Christian Ottmann12Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of TechnologyLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of TechnologyCystic Fibrosis Translational Research Centre, Department of Biochemistry and Physiology, McGill UniversityCyclenium Pharma Inc., 7171 rue Frederick BantingCyclenium Pharma Inc., 7171 rue Frederick BantingLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of TechnologyCystic Fibrosis Translational Research Centre, Department of Biochemistry and Physiology, McGill UniversityCystic Fibrosis Translational Research Centre, Department of Biochemistry and Physiology, McGill UniversityCyclenium Pharma Inc., 7171 rue Frederick BantingCyclenium Pharma Inc., 7171 rue Frederick BantingCyclenium Pharma Inc., 7171 rue Frederick BantingLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of TechnologyLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of TechnologyMutations in the chloride channel CFTR that impair plasma membrane insertion and ion transport are the cause of cystic fibrosis. Here, the authors identify a macrocycle that stabilizes the interaction of mutant CFTR with the chaperone-like protein 14-3-3 and rescues its biological function.https://doi.org/10.1038/s41467-022-31206-6 |
| spellingShingle | Loes M. Stevers Madita Wolter Graeme W. Carlile Dwight Macdonald Luc Richard Frank Gielkens John W. Hanrahan David Y. Thomas Sai Kumar Chakka Mark L. Peterson Helmut Thomas Luc Brunsveld Christian Ottmann Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR Nature Communications |
| title | Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR |
| title_full | Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR |
| title_fullStr | Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR |
| title_full_unstemmed | Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR |
| title_short | Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR |
| title_sort | macrocycle stabilization of its interaction with 14 3 3 increases plasma membrane localization and activity of cftr |
| url | https://doi.org/10.1038/s41467-022-31206-6 |
| work_keys_str_mv | AT loesmstevers macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT maditawolter macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT graemewcarlile macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT dwightmacdonald macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT lucrichard macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT frankgielkens macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT johnwhanrahan macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT davidythomas macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT saikumarchakka macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT marklpeterson macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT helmutthomas macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT lucbrunsveld macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr AT christianottmann macrocyclestabilizationofitsinteractionwith1433increasesplasmamembranelocalizationandactivityofcftr |