ABCMdb

PMID: 23284076

Hwang TC, Kirk KL
The CFTR ion channel: gating, regulation, and anion permeation.
Cold Spring Harb Perspect Med. 2013 Jan 1;3(1):a009498. doi: 10.1101/cshperspect.a009498., [PubMed]

Sentences

No. Mutations Sentence Comment

103 ABCC7 p.Gly551Asp This ATP-independent gating is readily seen with mutants with dysfunctional site 2 (e.g., the G551D mutation) (Bompadre et al. 2007), or interestingly constructs that lack the entire NBD2 (Cui et al. 2007; Wang et al. 2007). Login to comment 104 ABCC7 p.Gly551Asp Furthermore, gain-of-function (GOF) mutations that enhanceATP-free CFTR gating and increase the otherwise lowactivities of constructsthat are insensitive to ATP (G551D and NBD-deletion mutants) have been produced (Szollosi et al. 2010; Wang et al. 2010). Login to comment 115 ABCC7 p.Gly551Asp In addition, we foresee that understanding CFTR gating at a molecular level will shed light on the mechanism of action for therapeutic reagents such as Vx-770 (Kalydeco or ivacaftor), a recently FDA-approved CFTR potentiator for treating CF patients carrying the G551D mutation (Van Goor et al. 2009; Accurso et al. 2010; Ramsey et al. 2011). Login to comment 154 ABCC7 p.Gly551Asp Similarly, G551D-CFTR activity is dependent on PKA phosphorylation but not ATP binding (Bompadre et al. 2007; Wang et al. 2010). Login to comment 218 ABCC7 p.Lys95Ser Some K95 mutations (e.g., K95S) also markedly decrease singlechannelconductanceatbothdepolarizing and hyperpolarizing voltages (Zhou et al. 2010), which implies an effect on pore structure separate from a charge-attracting role for K95. Login to comment