ABCC7 p.Leu327Cys
| CF databases: |
c.980T>G
,
p.Leu327Arg
(CFTR1)
?
, This mutation is a substitution of T to G at position 1112 in nucleotide sequence and causes the replacement of a leucine by arginine residue in codon 327. This variation was observed by SSCP analysis during screening of CF samples for mutations. We are currently investigating wheter or not this alteration is a mutation or polymorphism.
|
| Predicted by SNAP2: | A: N (53%), C: N (61%), D: D (80%), E: D (71%), F: N (87%), G: D (71%), H: D (66%), I: N (72%), K: D (63%), M: N (72%), N: D (71%), P: D (80%), Q: D (63%), R: D (75%), S: D (63%), T: D (59%), V: N (93%), W: D (63%), Y: D (59%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: N, M: N, N: D, P: D, Q: N, R: D, S: D, T: N, V: N, W: D, Y: N, |
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[hide] Conformational changes in a pore-lining helix coup... J Biol Chem. 2008 Feb 22;283(8):4957-66. Epub 2007 Dec 3. Beck EJ, Yang Y, Yaemsiri S, Raghuram V
Conformational changes in a pore-lining helix coupled to cystic fibrosis transmembrane conductance regulator channel gating.
J Biol Chem. 2008 Feb 22;283(8):4957-66. Epub 2007 Dec 3., 2008-02-22 [PMID:18056267]
Abstract [show]
Cystic fibrosis transmembrane conductance regulator (CFTR), the protein dysfunctional in cystic fibrosis, is unique among ATP-binding cassette transporters in that it functions as an ion channel. In CFTR, ATP binding opens the channel, and its subsequent hydrolysis causes channel closure. We studied the conformational changes in the pore-lining sixth transmembrane segment upon ATP binding by measuring state-dependent changes in accessibility of substituted cysteines to methanethiosulfonate reagents. Modification rates of three residues (resides 331, 333, and 335) near the extracellular side were 10-1000-fold slower in the open state than in the closed state. Introduction of a charged residue by chemical modification at two of these positions (resides 331 and 333) affected CFTR single-channel gating. In contrast, modifications of pore-lining residues 334 and 338 were not state-dependent. Our results suggest that ATP binding induces a modest conformational change in the sixth transmembrane segment, and this conformational change is coupled to the gating mechanism that regulates ion conduction. These results may establish a structural basis of gating involving the dynamic rearrangement of transmembrane domains necessary for vectorial transport of substrates in ATP-binding cassette transporters.
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No. Sentence Comment
100 The oocytes 750 500 250 0 µS 180012006000 s IBMX MTSEA Cd 2+ DTT 200 100 0 µS 180012006000 s IBMX DTT Cd 2+ MTSEA A B C -100 -80 -60 -40 -20 0 20 40 % Change in conductance Y325C A326C L327C I328C K329C G330C I331C I332C L333C R334C K335C I336C F337C T338C T339C I340C S341C F342C WT I344C V345C R347C M348C A349C V350C T351C Q353C * * * * * Cd 2+ 1mM MTSEA 1mM D FIGURE 1.
X
ABCC7 p.Leu327Cys 18056267:100:195
status: NEW