PMID: 7515047

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., [PubMed]
Sentences
No. Mutations Sentence Comment
15 ABCC7 p.Arg347Glu
X
ABCC7 p.Arg347Glu 7515047:15:50
status: NEW
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ABCC7 p.Lys335Glu
X
ABCC7 p.Lys335Glu 7515047:15:38
status: NEW
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ABCC7 p.Lys95Asp
X
ABCC7 p.Lys95Asp 7515047:15:12
status: NEW
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Mutation of Lys-95 to Asp, in M1, and Lys-335 and Arg-347 to Glu, in M6, altered the permeability andlor conductance ratios for halides (6). Login to comment
16 ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 7515047:16:54
status: NEW
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ABCC7 p.Arg334Trp
X
ABCC7 p.Arg334Trp 7515047:16:61
status: NEW
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ABCC7 p.Arg347Pro
X
ABCC7 p.Arg347Pro 7515047:16:72
status: NEW
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Three mutationsassociated with mild clinical disease, R117H, R334W, and R347P,displayed altered single-channel properties (ll), but the structural basisof the functional changes is unknown. Login to comment
18 ABCC7 p.Arg347His
X
ABCC7 p.Arg347His 7515047:18:12
status: NEW
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Mutation of Arg-347 to His resulted in theability to eliminate themultiple ion occupancy effects by changing the pH of the intracellular solution, presumablyby titrating the stateof protonation of the histidine. Login to comment
69 ABCC7 p.Lys95Cys
X
ABCC7 p.Lys95Cys 7515047:69:131
status: NEW
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ABCC7 p.Gly91Cys
X
ABCC7 p.Gly91Cys 7515047:69:125
status: NEW
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ABCC7 p.Gln98Cys
X
ABCC7 p.Gln98Cys 7515047:69:141
status: NEW
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Application of the MTS reagents irreversibly alteredthe CFTR-induced currents of three of the cysteine substitution mutants, G91C, K95C, and Q98C. Login to comment
71 ABCC7 p.Gly91Cys
X
ABCC7 p.Gly91Cys 7515047:71:76
status: NEW
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2B and 3A).Application of MTSEA`for 1min irreversibly inhibited the mutants G91C by 43 * 6% (n = 5) (Figs. Login to comment
72 ABCC7 p.Lys95Cys
X
ABCC7 p.Lys95Cys 7515047:72:80
status: NEW
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ABCC7 p.Gln98Cys
X
ABCC7 p.Gln98Cys 7515047:72:15
status: NEW
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20 and 3C) and Q98C by 32 2 4% (n= 9) and potentiated the current of the mutant K95C by 108 2 22%(n = 4) (Figs. Login to comment
75 ABCC7 p.Lys95Cys
X
ABCC7 p.Lys95Cys 7515047:75:50
status: NEW
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ABCC7 p.Gly91Cys
X
ABCC7 p.Gly91Cys 7515047:75:59
status: NEW
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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). Login to comment
82 ABCC7 p.Lys95Cys
X
ABCC7 p.Lys95Cys 7515047:82:89
status: NEW
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The effect ofthe MTS reagentson wild typeCFTR and on thethreechannel-liningmutants GSlC, K95C,and QSSC. Login to comment
86 ABCC7 p.Lys95Cys
X
ABCC7 p.Lys95Cys 7515047:86:63
status: NEW
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ABCC7 p.Gly91Cys
X
ABCC7 p.Gly91Cys 7515047:86:72
status: NEW
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ABCC7 p.Gln98Cys
X
ABCC7 p.Gln98Cys 7515047:86:55
status: NEW
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A and C are from oocytesinjectedwith wild type CFTR B, Q98C; D,K95C; E, G91C. Login to comment
97 ABCC7 p.Lys95Cys
X
ABCC7 p.Lys95Cys 7515047:97:39
status: NEW
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The application ofMTSEA' to the mutant K95C increased the CFTR-induced current. Login to comment
101 ABCC7 p.Lys95Cys
X
ABCC7 p.Lys95Cys 7515047:101:21
status: NEW
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ABCC7 p.Lys95Cys
X
ABCC7 p.Lys95Cys 7515047:101:30
status: NEW
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1 MINMTS-EA, 8 MIN C K95C 5 D K95C 5 I -50 0 50 100 150-50 0 50 100 150 CHANGEINCURRENT (X) FIG.3. Login to comment
110 ABCC7 p.Lys95Cys
X
ABCC7 p.Lys95Cys 7515047:110:69
status: NEW
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ABCC7 p.Gly91Cys
X
ABCC7 p.Gly91Cys 7515047:110:64
status: NEW
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ABCC7 p.Gln98Cys
X
ABCC7 p.Gln98Cys 7515047:110:78
status: NEW
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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. Login to comment
122 ABCC7 p.Gly91Arg
X
ABCC7 p.Gly91Arg 7515047:122:200
status: NEW
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ABCC7 p.Gly91Cys
X
ABCC7 p.Gly91Cys 7515047:122:167
status: NEW
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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. Login to comment
123 ABCC7 p.Lys95Asp
X
ABCC7 p.Lys95Asp 7515047:123:132
status: NEW
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Effects on single-channel properties have been observed with other missense mutations associated with mild disease (11).Mutation of Lys-95 to Asp altered the relative anionper- meability sequence of the channel, although no evidence was presented that Lys-95 actually faced the channel lumen (6). Login to comment