Novel gain-of-function mutants identify a critical region within CFTR membrane-spanning domain 2 controlling cAMP-dependent and ATP-independent channel activation.

ABSTRACT: CFTR is an anion channel that has evolved from the mold of an ABC transporter. It possesses specific structural features, including a lateral portal between the cytoplasmic extensions of its transmembrane helices TM4 and TM6. This TM4-TM6 portal is lined by basic residues attracting anions from the cytosol towards the intracellular vestibule. Even though a symmetric, open portal is not observed at the level of the TM10/TM12 interface, basic amino acids are also present at this level, exposed to solvent in the vicinity of the regulatory R region, whose phosphorylation enables channel activation. Here, using all-atom molecular dynamics simulations in combination with functional and biochemical assays, we investigate the importance of these basic amino acids (R1158 and R1030), and of a neighb

SUBMITTER: Castanier S 

PROVIDER: S-EPMC11458853 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature