PMID: 9724537

Akabas MH
Channel-lining residues in the M3 membrane-spanning segment of the cystic fibrosis transmembrane conductance regulator.
Biochemistry. 1998 Sep 1;37(35):12233-40., 1998-09-01 [PubMed]
Sentences
No. Mutations Sentence Comment
97 ABCC7 p.Leu211Cys
X
ABCC7 p.Leu211Cys 9724537:97:173
status: NEW
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All of the mutants expressed cAMP-activated currents in FIGURE 2: MTS reagents do not inhibit currents induced by wild-type CFTR but they do inhibit currents induced by the L211C mutant. Login to comment
98 ABCC7 p.Leu211Cys
X
ABCC7 p.Leu211Cys 9724537:98:107
status: NEW
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Normalized current at -100 mV recorded from individual oocytes expressing wild-type CFTR (A and C) and the L211C mutant (B and D). Login to comment
105 ABCC7 p.Ala198Cys
X
ABCC7 p.Ala198Cys 9724537:105:220
status: NEW
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ABCC7 p.Pro205Cys
X
ABCC7 p.Pro205Cys 9724537:105:190
status: NEW
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The baseline conductance of the oocytes was generally less than 2.5 µS. The average cAMP-stimulated CFTR conductance for the cysteine-substitution mutants ranged between 49 µS for P205C and 142 µS for the A198C mutant (Figure 3A); for wild type the average conductance was 108 µS. The cAMP-stimulated current reached a plateau within 22 min in oocytes expressing wild-type CFTR. Login to comment
106 ABCC7 p.Ile203Cys
X
ABCC7 p.Ile203Cys 9724537:106:126
status: NEW
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ABCC7 p.Leu197Cys
X
ABCC7 p.Leu197Cys 9724537:106:95
status: NEW
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For the cysteine-substitution mutants the time to reach the plateau ranged from 19 min for the L197C mutant to 57 min for the I203C mutant (Figure 3B). Login to comment
107 ABCC7 p.Glu193Cys
X
ABCC7 p.Glu193Cys 9724537:107:132
status: NEW
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ABCC7 p.Asp192Cys
X
ABCC7 p.Asp192Cys 9724537:107:122
status: NEW
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It is interesting to note that all of the cysteine-substitution mutants that were not affected by the MTS reagents except D192C and E193C reached the plateau current in less than 30 min. Login to comment
113 ABCC7 p.Leu211Cys
X
ABCC7 p.Leu211Cys 9724537:113:161
status: NEW
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ABCC7 p.Pro205Cys
X
ABCC7 p.Pro205Cys 9724537:113:143
status: NEW
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ABCC7 p.Ile203Cys
X
ABCC7 p.Ile203Cys 9724537:113:136
status: NEW
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ABCC7 p.Phe200Cys
X
ABCC7 p.Phe200Cys 9724537:113:122
status: NEW
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ABCC7 p.Gln207Cys
X
ABCC7 p.Gln207Cys 9724537:113:150
status: NEW
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ABCC7 p.His199Cys
X
ABCC7 p.His199Cys 9724537:113:115
status: NEW
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ABCC7 p.Trp202Cys
X
ABCC7 p.Trp202Cys 9724537:113:129
status: NEW
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In contrast, a 1-min application of 10 mM MTSES- significantly inhibited the CFTR-induced currents for the mutants H199C, F200C, W202C, I203C, P205C, Q207C, and L211C (Figure 4). Login to comment
119 ABCC7 p.Leu214Cys
X
ABCC7 p.Leu214Cys 9724537:119:76
status: NEW
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In addition, a 1-min application of 2.5 mM MTSEA+ also inhibited the mutant L214C (Figure 5). Login to comment
167 ABCC7 p.His199Cys
X
ABCC7 p.His199Cys 9724537:167:104
status: NEW
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Thus, in order for the MTS reagents to reach the most cytoplasmic accessible residue in the M3 segment, H199C, the channel must be at least 6 Å in diameter from the extracellular end to the level of His199. Login to comment
200 ABCC7 p.Pro205Ser
X
ABCC7 p.Pro205Ser 9724537:200:13
status: NEW
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The mutation P205S is associated with mild CF (58); this and other mutations of Pro205 reduce the formation of mature CFTR protein but they do not alter the halide permeability and conductance ratios (31). Login to comment
222 ABCC7 p.Pro205Ser
X
ABCC7 p.Pro205Ser 9724537:222:152
status: NEW
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ABCC7 p.Leu206Trp
X
ABCC7 p.Leu206Trp 9724537:222:163
status: NEW
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ABCC7 p.His199Tyr
X
ABCC7 p.His199Tyr 9724537:222:145
status: NEW
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ABCC7 p.Glu193Lys
X
ABCC7 p.Glu193Lys 9724537:222:138
status: NEW
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ABCC7 p.Asp192Gly
X
ABCC7 p.Asp192Gly 9724537:222:131
status: NEW
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Several mutations of residues in and flanking the M3 membrane-spanning segment have been identified in patients with CF, including D192G, E193K, H199Y, P205S, and L206W (58, 60-63). Login to comment