ABCC7 p.Gly91Cys
| ClinVar: |
c.271G>A
,
p.Gly91Arg
D
, Pathogenic
|
| CF databases: |
c.271G>A
,
p.Gly91Arg
(CFTR1)
D
, This mutation was observed through DGGE screening and direct DNA sequencing. The substitution is a G->A at nucleotide position 403. It changes a glycine residue for an arginine G91R. The haplotype bearing the mutation is a C haplotype. The CF child has a [delta]F508 on th other chromosome. He is 9 years old and pancreatic sufficient. The substitution was observed once on 87 non-[delta]F508 chromosomes and non oberved on 70 [delta]F508 chromosomes.
|
| Predicted by SNAP2: | A: D (75%), C: D (85%), D: D (91%), E: D (91%), F: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (91%), M: D (95%), N: D (91%), P: D (95%), Q: D (91%), R: D (59%), S: D (85%), T: D (85%), V: D (85%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | A: N, C: D, D: N, E: N, F: D, H: N, I: D, K: D, L: D, M: D, N: N, P: D, Q: N, R: D, S: N, T: N, V: D, W: D, Y: N, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] CFTR: mechanism of anion conduction. Physiol Rev. 1999 Jan;79(1 Suppl):S47-75. Dawson DC, Smith SS, Mansoura MK
CFTR: mechanism of anion conduction.
Physiol Rev. 1999 Jan;79(1 Suppl):S47-75., [PMID:9922376]
Abstract [show]
CFTR: Mechanism of Anion Conduction. Physiol. Rev. 79, Suppl.: S47-S75, 1999. - The purpose of this review is to collect together the results of recent investigations of anion conductance by the cystic fibrosis transmembrane conductance regulator along with some of the basic background that is a prerequisite for developing some physical picture of the conduction process. The review begins with an introduction to the concepts of permeability and conductance and the Nernst-Planck and rate theory models that are used to interpret these parameters. Some of the physical forces that impinge on anion conductance are considered in the context of permeability selectivity and anion binding to proteins. Probes of the conduction process are considered, particularly permeant anions that bind tightly within the pore and block anion flow. Finally, structure-function studies are reviewed in the context of some predictions for the origin of pore properties.
Comments [show]
None has been submitted yet.
No. Sentence Comment
475 In three TM1 mutants, G91C, K95C, Q98C, all of which fall on the same face of a predicted TM1 a- ter`` is close to the cytoplasmic end of the pore and that R352 may play a role in determining charge selectivity forhelix, the conductance was irreversibly altered by either MTSES0 or MTSEA0 .
X
ABCC7 p.Gly91Cys 9922376:475:22
status: NEW[hide] Cystic fibrosis transmembrane conductance regulato... Biophys J. 1998 Mar;74(3):1320-32. Mansoura MK, Smith SS, Choi AD, Richards NW, Strong TV, Drumm ML, Collins FS, Dawson DC
Cystic fibrosis transmembrane conductance regulator (CFTR) anion binding as a probe of the pore.
Biophys J. 1998 Mar;74(3):1320-32., [PMID:9512029]
Abstract [show]
We compared the effects of mutations in transmembrane segments (TMs) TM1, TM5, and TM6 on the conduction and activation properties of the cystic fibrosis transmembrane conductance regulator (CFTR) to determine which functional property was most sensitive to mutations and, thereby, to develop a criterion for measuring the importance of a particular residue or TM for anion conduction or activation. Anion substitution studies provided strong evidence for the binding of permeant anions in the pore. Anion binding was highly sensitive to point mutations in TM5 and TM6. Permeability ratios, in contrast, were relatively unaffected by the same mutations, so that anion binding emerged as the conduction property most sensitive to structural changes in CFTR. The relative insensitivity of permeability ratios to CFTR mutations was in accord with the notion that anion-water interactions are important determinants of permeability selectivity. By the criterion of anion binding, TM5 and TM6 were judged to be likely to contribute to the structure of the anion-selective pore, whereas TM1 was judged to be less important. Mutations in TM5 and TM6 also dramatically reduced the sensitivity of CFTR to activation by 3-isobutyl 1-methyl xanthine (IBMX), as expected if these TMs are intimately involved in the physical process that opens and closes the channel.
Comments [show]
None has been submitted yet.
No. Sentence Comment
270 In fact, the data presented by Akabas et al. (1994) suggest that the activation of the G91C mutant was markedly slowed compared with that of wtCFTR.
X
ABCC7 p.Gly91Cys 9512029:270:87
status: NEW[hide] Amino acid residues lining the chloride channel of... J Biol Chem. 1994 May 27;269(21):14865-8. Akabas MH, Kaufmann C, Cook TA, Archdeacon P
Amino acid residues lining the chloride channel of the cystic fibrosis transmembrane conductance regulator.
J Biol Chem. 1994 May 27;269(21):14865-8., [PMID:7515047]
Abstract [show]
The cystic fibrosis transmembrane conductance regulator forms a chloride channel that is regulated by phosphorylation and intracellular ATP levels. The structure of the channel-forming domains is undetermined. To identify the residues lining this channel we substituted cysteine, one at a time, for 9 consecutive residues (91-99) in the M1 membrane-spanning segment. The cysteine substitution mutants were expressed in Xenopus oocytes. We determined the accessibility of the engineered cysteine to charged, sulfhydryl-specific methanethiosulfonate reagents added extracellularly. We assume that, among residues in membrane-spanning segments, only those lining the channel will be accessible to react with these hydrophilic reagents and that such a reaction would irreversibly alter conduction through the channel. Only the cysteines substituted for Gly-91, Lys-95, and Gln-98 were accessible to the reagents. We conclude that these residues are in the channel lining. The periodicity of these residues is consistent with an alpha-helical secondary structure.
Comments [show]
None has been submitted yet.
No. Sentence Comment
69 Application of the MTS reagents irreversibly alteredthe CFTR-induced currents of three of the cysteine substitution mutants, G91C, K95C, and Q98C.
X
ABCC7 p.Gly91Cys 7515047:69:125
status: NEW71 2B and 3A).Application of MTSEA`for 1min irreversibly inhibited the mutants G91C by 43 * 6% (n = 5) (Figs.
X
ABCC7 p.Gly91Cys 7515047:71:76
status: NEW75 The anionic reagent, MTSES-, had no effect on the K95C and G91C mutants (Fig. 3,A andB).To determine whether thelack of effect was due to inability to react with Cys-95 or lack of effect followingreaction, we sequentially applied MTSES- and MTSEA+;MTSES- did not prevent the potentiationof the current by MTSEA+(data notshown).
X
ABCC7 p.Gly91Cys 7515047:75:59
status: NEW86 A and C are from oocytesinjectedwith wild type CFTR B, Q98C; D,K95C; E, G91C.
X
ABCC7 p.Gly91Cys 7515047:86:72
status: NEW110 Based on the accessibility of the cysteine-substitution mutants G91C,K95C and Q98C to the MTS reagents, we infer that the side chains of the corresponding wild type residues, Gly-91,Lys-95, and Gln-98, line the channel ofCFTR.
X
ABCC7 p.Gly91Cys 7515047:110:64
status: NEW122 Although the Arg side chain is somewhat larger than theside chain of Cys modified by MTSEA', the reduction in whole cell current we observed following modification of G91C by MTSEA' suggests that the G91R mutant will have altered single-channel properties.
X
ABCC7 p.Gly91Cys 7515047:122:167
status: NEW