Proteostasis landscapes of cystic fibrosis variants reveal drug response vulnerability.

ABSTRACT: Cystic fibrosis (CF) is a lethal genetic disorder caused by variants in CF transmembrane conductance regulator (CFTR). Many variants are treatable with correctors, which enhance the folding and trafficking of CFTR. However, approximately 3% of persons with CF harbor poorly responsive variants. Here, we used affinity purification mass spectrometry proteomics to profile the protein homeostasis (proteostasis) changes of CFTR variants during correction to assess modulated interactions with protein folding and maturation pathways. Responsive variant interactions converged on similar proteostasis pathways during correction. In contrast, poorly responsive variants subtly diverged, revealing a partial restoration of protein quality control surveillance and partial correction. Computational structu

SUBMITTER: McDonald EF 

PROVIDER: S-EPMC12054793 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature