Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR.
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ABSTRACT:
SUBMITTER: Stevers LM
PROVIDER: S-EPMC9226124 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
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Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR.
Stevers Loes M LM Wolter Madita M Carlile Graeme W GW Macdonald Dwight D Richard Luc L Gielkens Frank F Hanrahan John W JW Thomas David Y DY Chakka Sai Kumar SK Peterson Mark L ML Thomas Helmut H Brunsveld Luc L Ottmann Christian C
Nature communications 20220623 1
Impaired activity of the chloride channel CFTR is the cause of cystic fibrosis. 14-3-3 proteins have been shown to stabilize CFTR and increase its biogenesis and activity. Here, we report the identification and mechanism of action of a macrocycle stabilizing the 14-3-3/CFTR complex. This molecule rescues plasma membrane localization and chloride transport of F508del-CFTR and works additively with the CFTR pharmacological chaperone corrector lumacaftor (VX-809) and the triple combination Trikafta ...[more]
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