Home
Browse
Search
Statistics
About
Usage
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
view ABCC7 p.Leu211Cys details
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
view ABCC7 p.Leu211Cys details
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
view ABCC7 p.Ala198Cys details
ABCC7 p.Pro205Cys
X
ABCC7 p.Pro205Cys 9724537:105:190
status:
NEW
view ABCC7 p.Pro205Cys details
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
view ABCC7 p.Ile203Cys details
ABCC7 p.Leu197Cys
X
ABCC7 p.Leu197Cys 9724537:106:95
status:
NEW
view ABCC7 p.Leu197Cys details
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
view ABCC7 p.Glu193Cys details
ABCC7 p.Asp192Cys
X
ABCC7 p.Asp192Cys 9724537:107:122
status:
NEW
view ABCC7 p.Asp192Cys details
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
view ABCC7 p.Leu211Cys details
ABCC7 p.Pro205Cys
X
ABCC7 p.Pro205Cys 9724537:113:143
status:
NEW
view ABCC7 p.Pro205Cys details
ABCC7 p.Ile203Cys
X
ABCC7 p.Ile203Cys 9724537:113:136
status:
NEW
view ABCC7 p.Ile203Cys details
ABCC7 p.Phe200Cys
X
ABCC7 p.Phe200Cys 9724537:113:122
status:
NEW
view ABCC7 p.Phe200Cys details
ABCC7 p.Gln207Cys
X
ABCC7 p.Gln207Cys 9724537:113:150
status:
NEW
view ABCC7 p.Gln207Cys details
ABCC7 p.His199Cys
X
ABCC7 p.His199Cys 9724537:113:115
status:
NEW
view ABCC7 p.His199Cys details
ABCC7 p.Trp202Cys
X
ABCC7 p.Trp202Cys 9724537:113:129
status:
NEW
view ABCC7 p.Trp202Cys details
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
view ABCC7 p.Leu214Cys details
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
view ABCC7 p.His199Cys details
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
view ABCC7 p.Pro205Ser details
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
view ABCC7 p.Pro205Ser details
ABCC7 p.Leu206Trp
X
ABCC7 p.Leu206Trp 9724537:222:163
status:
NEW
view ABCC7 p.Leu206Trp details
ABCC7 p.His199Tyr
X
ABCC7 p.His199Tyr 9724537:222:145
status:
NEW
view ABCC7 p.His199Tyr details
ABCC7 p.Glu193Lys
X
ABCC7 p.Glu193Lys 9724537:222:138
status:
NEW
view ABCC7 p.Glu193Lys details
ABCC7 p.Asp192Gly
X
ABCC7 p.Asp192Gly 9724537:222:131
status:
NEW
view ABCC7 p.Asp192Gly details
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