ABCMdb

PMID: 7539989

Gadsby DC, Nagel G, Hwang TC
The CFTR chloride channel of mammalian heart.
Annu Rev Physiol. 1995;57:387-416., [PubMed]

Sentences

No. Mutations Sentence Comment

18 ABCC7 p.Lys335Glu ABCC7 p.Lys95Asp For example, expression in 3T3 cells of two CFTR mutants, K95D and K335E, in which negatively charged amino acids replaced positively charged lysines in the first (Ml) and sixth (M6) putative transmembrane a-helices (Figure I) yielded Cl- channels with altered anion permeability sequences, 1- > B..- > Cl- instead of the normal Br > CI- > 1- (3). Login to comment 19 ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro Also, three missense mutations associated with relatively mild CF disease, two (R334W and R347P) neutralizing positively charged arginines in M6 and one (Rl19H) substituting histidine for an arginine near the extracellular end of M2, all diminish open-channel conductance (120). Login to comment 20 ABCC7 p.Arg347His ABCC7 p.Arg347Asp The conclusion that certain residues in M l and M6 line the anion-selective pore is corroborated by three new pieces of evidence: (a) Tabcharani et al (130) found that the charge-switching mutation R347D lowered channel conductance and abolished the anomalous mole-fraction effect seen with mixtures of CI- and SCN- ions, and that channel conductance and anomalous mole-fraction behavior became pH sensitive in the mutant R347H. Login to comment 110 ABCC7 p.Lys1250Met The conclusion is that ATP hydrolysis, most likely at NBD1 (because ATP regulates gating of an NBD2 mutant, K1250M), is required to open CFfR channels (2). Login to comment