ABCC7 p.Arg1128Glu
| ClinVar: |
c.3382A>T
,
p.Arg1128*
?
, not provided
|
| Predicted by SNAP2: | A: D (63%), C: D (75%), D: D (66%), E: N (57%), F: D (85%), G: D (71%), H: D (63%), I: D (53%), K: N (57%), L: D (63%), M: D (75%), N: N (53%), P: D (80%), Q: N (72%), S: D (53%), T: N (53%), V: D (53%), W: D (91%), Y: D (80%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Identification of positive charges situated at the... Pflugers Arch. 2008 Nov;457(2):351-60. Epub 2008 May 1. Zhou JJ, Fatehi M, Linsdell P
Identification of positive charges situated at the outer mouth of the CFTR chloride channel pore.
Pflugers Arch. 2008 Nov;457(2):351-60. Epub 2008 May 1., [PMID:18449561]
Abstract [show]
We have used site-directed mutagenesis and functional analysis to identify positively charged amino acid residues in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel that interact with extracellular anions. Mutation of two positively charged arginine residues in the first extracellular loop (ECL) of CFTR, R104, and R117, as well as lysine residue K335 in the sixth transmembrane region, leads to inward rectification of the current-voltage relationship and decreased single channel conductance. These effects are dependent on the charge of the substituted side chain and on the Cl(-) concentration, suggesting that these positive charges normally act to concentrate extracellular Cl(-) ions near the outer mouth of the pore. Side chain charge-dependent effects are mimicked by manipulating charge in situ by mutating these amino acids to cysteine followed by covalent modification with charged cysteine-reactive reagents, confirming the location of these side chains within the pore outer vestibule. State-independent modification of R104C and R117C suggests that these residues are located at the outermost part of the pore. We suggest that ECL1 contributes to the CFTR pore external vestibule and that positively charged amino acid side chains in this region act to attract Cl(-) ions into the pore. In contrast, we find no evidence that fixed positive charges in other ECLs contribute to the permeation properties of the pore.
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No. Sentence Comment
60 As shown in Fig. 2, similar inward rectification is observed in the charge-reversing mutants R104E, R117E, and K335E and to a much lesser extent, R1128E, under symmetrical ionic conditions in excised membrane patches.
X
ABCC7 p.Arg1128Glu 18449561:60:146
status: NEW78 The mutations K114E, K329E, K892E, R899E, and R1128E did not affect unitary current amplitude at any voltage (Fig. 4b), consistent with these residues not being involved in Cl- permeation.
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ABCC7 p.Arg1128Glu 18449561:78:46
status: NEW91 All mutants depicted (R104Q, R117Q, K335A, R1128Q, R104E, R117E, K335E, R1128E) showed rectification ratios significantly different from wild type (asterisk P<0.05).
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ABCC7 p.Arg1128Glu 18449561:91:72
status: NEW