ABCC7 p.Cys343Thr
| CF databases: |
c.1029delC
,
p.Cys343*
D
, CF-causing
|
| Predicted by SNAP2: | A: N (78%), D: D (66%), E: D (63%), F: D (63%), G: N (53%), H: D (59%), I: D (63%), K: D (66%), L: D (63%), M: D (63%), N: N (66%), P: D (71%), Q: D (63%), R: D (53%), S: N (78%), T: N (66%), V: D (53%), W: D (75%), Y: D (59%), |
| Predicted by PROVEAN: | A: N, D: D, E: D, F: N, G: D, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: D, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Functional Differences in Pore Properties Between ... J Membr Biol. 2011 Oct;243(1-3):15-23. Epub 2011 Jul 28. Holstead RG, Li MS, Linsdell P
Functional Differences in Pore Properties Between Wild-Type and Cysteine-Less Forms of the CFTR Chloride Channel.
J Membr Biol. 2011 Oct;243(1-3):15-23. Epub 2011 Jul 28., [PMID:21796426]
Abstract [show]
Studies of the structure and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel have been advanced by the development of functional channel variants in which all 18 endogenous cysteine residues have been mutated ("cys-less" CFTR). However, cys-less CFTR has a slightly higher single-channel conductance than wild-type CFTR, raising questions as to the suitability of cys-less as a model of the wild-type CFTR pore. We used site-directed mutagenesis and patch-clamp recording to investigate the origin of this conductance difference and to determine the extent of functional differences between wild-type and cys-less CFTR channel permeation properties. Our results suggest that the conductance difference is the result of a single substitution, of C343: the point mutant C343S has a conductance similar to cys-less, whereas the reverse mutation, S343C in a cys-less background, restores wild-type conductance levels. Other cysteine substitutions (C128S, C225S, C376S, C866S) were without effect. Substitution of other residues for C343 suggested that conductance is dependent on amino acid side chain volume at this position. A range of other functional pore properties, including interactions with channel blockers (Au[CN] (2) (-) , 5-nitro-2-[3-phenylpropylamino]benzoic acid, suramin) and anion permeability, were not significantly different between wild-type and cys-less CFTR. Our results suggest that functional differences between these two CFTR constructs are of limited scale and scope and result from a small change in side chain volume at position 343. These results therefore support the use of cys-less as a model of the CFTR pore region.
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No. Sentence Comment
67 As shown in Fig. 3, single-channel conductance was significantly reduced in C343L, significantly increased in C343A as well as C343S and not significantly changed in C343T and C343V.
X
ABCC7 p.Cys343Thr 21796426:67:166
status: NEW138 Since C343T (unlike C343S) was not associated with a significant change in single-channel conductance (Fig. 3), a cys-less construct in which C343 is replaced by threonine, rather than serine, might be considered to retain wild-type channel properties more faithfully.
X
ABCC7 p.Cys343Thr 21796426:138:6
status: NEW