ABCC7 p.Tyr380Cys
| Predicted by SNAP2: | A: N (57%), C: N (72%), D: N (53%), E: N (61%), F: N (93%), G: N (53%), H: N (87%), I: N (82%), K: N (61%), L: N (82%), M: N (78%), N: N (66%), P: D (53%), Q: N (78%), R: N (72%), S: N (66%), T: N (66%), V: N (78%), W: N (82%), |
| Predicted by PROVEAN: | A: N, C: N, D: D, E: N, F: N, G: D, H: N, I: N, K: D, L: N, M: N, N: D, P: D, Q: N, R: N, S: N, T: N, V: N, W: N, |
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[hide] CFTR: covalent and noncovalent modification sugges... J Gen Physiol. 2001 Oct;118(4):407-31. Smith SS, Liu X, Zhang ZR, Sun F, Kriewall TE, McCarty NA, Dawson DC
CFTR: covalent and noncovalent modification suggests a role for fixed charges in anion conduction.
J Gen Physiol. 2001 Oct;118(4):407-31., [PMID:11585852]
Abstract [show]
The goal of the experiments described here was to explore the possible role of fixed charges in determining the conduction properties of CFTR. We focused on transmembrane segment 6 (TM6) which contains four basic residues (R334, K335, R347, and R352) that would be predicted, on the basis of their positions in the primary structure, to span TM6 from near the extracellular (R334, K335) to near the intracellular (R347, R352) end. Cysteines substituted at positions 334 and 335 were readily accessible to thiol reagents, whereas those at positions 347 and 352 were either not accessible or lacked significant functional consequences when modified. The charge at positions 334 and 335 was an important determinant of CFTR channel function. Charge changes at position 334--brought about by covalent modification of engineered cysteine residues, pH titration of cysteine and histidine residues, and amino acid substitution--produced similar effects on macroscopic conductance and the shape of the I-V plot. The effect of charge changes at position 334 on conduction properties could be described by electrodiffusion or rate-theory models in which the charge on this residue lies in an external vestibule of the pore where it functions to increase the concentration of Cl adjacent to the rate-limiting portion of the conduction path. Covalent modification of R334C CFTR increased single-channel conductance determined in detached patches, but did not alter open probability. The results are consistent with the hypothesis that in wild-type CFTR, R334 occupies a position where its charge can influence the distribution of anions near the mouth of the pore.
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No. Sentence Comment
483 The conductance of oocytes expressing the I379C construct was reduced by MTS reagents (MTSET, MTSEA, and MTSES) regardless of charge, whereas the effects of the same reagents on oocytes expressing the Y380C construct were distinctly charge-dependent.
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ABCC7 p.Tyr380Cys 11585852:483:201
status: NEW484 The anionic reagent (MTSES) increased the macroscopic conductance of oocytes expressing Y380C and altered the shape of the I-V plot from outwardly rectifying to nearly linear, whereas cationic reagents (MTSET and MTSEA) reduced the conductance and enhanced the rectification, exactly as predicted for a residue that resides near the mouth of a cation-selective pore.
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ABCC7 p.Tyr380Cys 11585852:484:88
status: NEW485 Single-channel records disclosed that MTS reagents altered the unitary conductance of Y380C channels as would be predicted from macroscopic records, but did not affect channel gating.
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ABCC7 p.Tyr380Cys 11585852:485:86
status: NEW