ABCMdb

PMID: 21296873

Kirk KL, Wang W
A unified view of cystic fibrosis transmembrane conductance regulator (CFTR) gating: combining the allosterism of a ligand-gated channel with the enzymatic activity of an ATP-binding cassette (ABC) transporter.
J Biol Chem. 2011 Apr 15;286(15):12813-9. Epub 2011 Feb 4., 2011-04-15 [PubMed]

Sentences

No. Mutations Sentence Comment

99 ABCC7 p.Gly551Asp Hwang and co-workers (50) also noted that channel openings could be detected for a CF mutant form of CFTR that is completely unresponsive to ATP (G551D mutation in NBD1 signature sequence). Login to comment 107 ABCC7 p.Gly551Asp The conclusion that the cytosolic loop mutations enhance unliganded CFTR Po is further supported by their abilities to enhance the otherwise low activities of CFTR-G551D and CFTR⌬1198 (NBD2 deletion construct) channels when introduced into these ATP-insensitive constructs (51). Login to comment 134 ABCC7 p.Lys978Cys The strongest evidence for the latter is the observation that CFTR channels that lack NBD2 but possess one of the constitutive loop mutations (e.g. CFTR-K978C/⌬1198) are strongly stimulated by PKA phosphorylation of the R domain even 4 Regarding Fig. 4A, it is important to note that we do not consider the open pore conformation at the TMDs (whatever that looks like structurally) to be strictly demanded by a tight NBD1-NBD2 dimer, nor do we consider the closed pore conformation to be demanded by the absence of the NBD1-NBD2 dimer. Login to comment 174 ABCC7 p.Gly551Asp The rescue of CFTR-G551D function by constitutive mutations in the cytosolic loops supports this concept (51). Login to comment 175 ABCC7 p.Gly551Asp Some of the small molecule activators of mutant CFTR channels such as G551D that have been discovered recently (63, 64) may target the cytosolic loops or TMDs along the channel symmetry axis to promote unliganded activity. Login to comment