ABCB1 p.Val71Arg
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PMID: 18596043
[PubMed]
Loo TW et al: "Arginines in the first transmembrane segment promote maturation of a P-glycoprotein processing mutant by hydrogen bond interactions with tyrosines in transmembrane segment 11."
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Sentence
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55
For disulfide cross-linking analysis, the cDNA of mutant L339C(TM6)/F728C(TM7) (16) was modified to also encode the G64R, M68R, or V71R mutations.
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ABCB1 p.Val71Arg 18596043:55:131
status: NEW104 Mutants G64R and V71R showed maturation efficiencies of FIGURE 1.
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ABCB1 p.Val71Arg 18596043:104:17
status: NEW156 Because the G64R and V71R changes also promoted maturation of the G251V processing mutant (Fig. 2), we also introduced these mutations into the L339C(TM6)/F728C(TM7) mutant.
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ABCB1 p.Val71Arg 18596043:156:21
status: NEW165 TABLE 1 Effects of drug substrates on the maturation of TM1 arginine mutants containing the G251V mutation Mutation (G251V ؉) No drug Cyclosporin A Verapamil Vinblastine Rhodamine None - 111a,c 111 111 11 V52R -a,b 111 111 111 11 V53R 2 - - - - G64R 2 - - - - T55R 2 - - - - L56R 2 - - - - A57R 2 - - - - A58R 2 - - - - I59R 2 - - - - I60R 2 - - - - H61R - 111 1 1 1 G62R 2 - - - - A63R 2 - - - - G64R 1 111 1 1 11 L65R 11 111 11 11 11 P66R 2 1 - - - L67R - 111 111 111 11 M68R 111 111 111 111 111 M69R - 111 - 11 111 L70R - 111 111 111 11 V71R 1 111 111 111 11 F72R 2 1 1 1 1 a Change in the amount of mature (170 kDa) protein in the presence of drug substrate relative to that in the absence of drug substrate.
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ABCB1 p.Val71Arg 18596043:165:546
status: NEW173 Membranes were prepared from HEK 293 cells expressing mutants L339C(TM6)/F728C(TM7), G64R/ L339C(TM6)/F728C(TM7), M68R/ L339C(TM6)/F728C(TM7), and V71R/L339C(TM6)/F728C(TM7).
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ABCB1 p.Val71Arg 18596043:173:147
status: NEW181 The G64R/L339C(TM6)/ F728C(TM7) mutant also showed a large reduction in apparent affinity for vinblastine (Ͼ100-fold), whereas the V71R change had little effect.
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ABCB1 p.Val71Arg 18596043:181:137
status: NEW194 TABLE 2 Concentrations of drug substrates required to inhibit cross-linking by 50% Mutant Vinblastine Cyclosporin A Rhodamine B M M M L339C/F728C 0.5 Ϯ 0.2a 0.8 Ϯ 0.3 52 Ϯ 14 G64R/L339C/F728C 53 Ϯ 15b 1.5 Ϯ 0.4 61 Ϯ 10 M68R/L339C/F728C 266 Ϯ 62b 1.3 Ϯ 0.3 57 Ϯ 7 V71R/L339C/F728C 0.6 Ϯ 0.2 0.8 Ϯ 0.2 57 Ϯ 10 a Each value is the mean Ϯ S.D. (n ϭ 3-4 separate cross-linking experiments).
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ABCB1 p.Val71Arg 18596043:194:341
status: NEW278 Residue Val-71, however, appeared to lie outside the drug binding pocket since the V71R mutation did not affect P-gp-drug interactions (Table 3).
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ABCB1 p.Val71Arg 18596043:278:83
status: NEW298 Some mutations such as G64R, L65R, M68R, and V71R actually promoted maturation of the G251V mutant.
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ABCB1 p.Val71Arg 18596043:298:45
status: NEW