Structural basis for CFTR inhibition by CFTR_inh-172.

ABSTRACT: The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that regulates electrolyte and fluid balance in epithelial tissues. While activation of CFTR is vital to treating cystic fibrosis, selective inhibition of CFTR is a potential therapeutic strategy for secretory diarrhea and autosomal dominant polycystic kidney disease. Although several CFTR inhibitors have been developed by high-throughput screening, their modes of action remain elusive. In this study, we determined the structure of CFTR in complex with the inhibitor CFTR_inh-172 to an overall resolution of 2.7 Å by cryogenic electron microscopy. We observe that CFTR_inh-172 binds inside the pore near transmembrane helix 8, a critical structural element that links adenosine triphosphate hy

SUBMITTER: Young PG 

PROVIDER: S-EPMC10927578 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature