ABCB1 p.Thr55Arg

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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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142 Therefore, mutants showing reduced (T55R/G251V) or similar maturation efficiencies (H61R/G251V, M69R/G251V) to the G251V parent were expressed in the presence of 5 ␮M cyclosporin A, 30 ␮M verapamil, 5 ␮M vinblastine, or 30 ␮M rhodamine B.
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ABCB1 p.Thr55Arg 18596043:142:36
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144 By contrast, a mutant where the introduced arginine inhibited maturation of G251V (mutant T55R) could not be rescued with any of the drug substrates (Fig. 5).
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ABCB1 p.Thr55Arg 18596043:144:90
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151 By contrast, 12 of the mutants (V53R, G54R, T55R, L56R, A57R, A58R, I59R, I60R, G62R, A63R, P66R, and F72R) showed little or no rescue in the presence of drug substrates.
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ABCB1 p.Thr55Arg 18596043:151:44
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163 HEK 293 cells expressing mutants G251V, T55R/G251V, H61R/G251V, or M69R/G251V were treated with no drug (None), 5 ␮M cyclosporin A (Cyclo), 30 ␮M verapamil (Ver), 5 ␮M vinblastine (Vin), or 30 ␮M rhodamine B (Rhod) for 24 h. Whole cell extracts were then subjected to immunoblot analysis.
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ABCB1 p.Thr55Arg 18596043:163:40
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165 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.Thr55Arg 18596043:165:266
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PMID: 22232552 [PubMed] Iram SH et al: "Mutation of Glu521 or Glu535 in cytoplasmic loop 5 causes differential misfolding in multiple domains of multidrug and organic anion transporter MRP1 (ABCC1)."
No. Sentence Comment
261 Thus, the P-glycoprotein processing mutant G251V/T55R is not rescued by any drug substrates, whereas another mutant G251V/H61R can be rescued by only a single substrate (cyclosporine A) (39).
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ABCB1 p.Thr55Arg 22232552:261:49
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