ABCMdb

PMID: 9558482

Foskett JK
ClC and CFTR chloride channel gating.
Annu Rev Physiol. 1998;60:689-717., [PubMed]

Sentences

No. Mutations Sentence Comment

289 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly1349Asp In CFTR, mutation of G551 or G1349 to aspartic acid (G551D, G1349D; both are CF mutations), decreases ATP binding (149) and the G551D mutation inhibits ATP hydrolysis (151). Login to comment 307 ABCC7 p.Lys464Ala In one study, ATP hydrolysis by a recombinant NBD1-maltose-binding protein fusion protein was inhibited by replacement of the Walker A lysine with alanine (K464A) (179), confirming predictions. Login to comment 308 ABCC7 p.Lys464Ala K464A CFTR channels have reduced Po (135, 145). Login to comment 314 ABCC7 p.Lys464Ala Activation of D572 and G551 mutants is inhibited (153, 154), and channel gating of Q552 mutants is altered (138) similarly to those for the K464A mutant. Login to comment 321 ABCC7 p.Lys1250Ala The prolonged openings observed in the K1250A mutant are distinguished from those induced by nonhydrolyzable ATP analogues because they are independent of the degree of channel phosphorylation (145), whereas nonhydrolyzable analogues may only affect fully phosphorylated channels (127). Login to comment 323 ABCC7 p.His1350Gln ABCC7 p.His1350Ala Mutation of this residue to glutamine (H1350Q; predicted to increase ATP hydrolysis rate) but not to alanine (H1350A; predicted to have no effect on hydrolysis) destabilized the open state (138), again supporting a role for hydrolysis at NBD2 in controlling the duration of the open state. Login to comment 324 ABCC7 p.Lys1250Ala ABCC7 p.Asp1370Asn An interesting contrast to the effects of the K1250A mutation in the Walker A motif was revealed in a D1370N mutant in the Walker B motif. Login to comment 325 ABCC7 p.Lys1250Ala ABCC7 p.Lys1250Ala In the latter, openings as well as closings were prolonged, but the prolonged openings (≈1.5 s) were considerably shorter than those seen in the K1250A mutant (tens of seconds) (150). Login to comment 329 ABCC7 p.Lys1250Ala Furthermore, they suggest that the prolonged openings induced by polyphosphates and the K1250A mutation require Mg2+ and nucleotide binding at NBD2. Login to comment 331 ABCC7 p.Gly1249Glu ABCC7 p.Gly1247Asp Mutations predicted to abolish nucleotide binding at NBD2, a G1247D/G1249E double mutant, exhibit low Po because of extended closed times and only brief openings (to O1 only), which are independent of ATP (150). Login to comment