ABCC1 p.Arg1142Lys
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PMID: 16230346
[PubMed]
Conseil G et al: "Functional importance of three basic residues clustered at the cytosolic interface of transmembrane helix 15 in the multidrug and organic anion transporter MRP1 (ABCC1)."
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Sentence
Comment
122
B, HEK293T cells were transfected with expression vectors encoding WT-MRP1 and MRP1 mutants R1138E, R1138K, K1141E, K1141R, R1142E, and R1142K, and 48 h later, cells were probed with monoclonal antibody QCRL-3 and processed for confocal fluorescence microscopy using Alexa Fluor 488 conjugated secondary antibody.
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ABCC1 p.Arg1142Lys 16230346:122:136
status: NEW132 A same charge substitution of Arg1138 and Lys1141 had no effect, whereas the E217betaG transport activity of the R1142K mutant was reduced by ϳ35%.
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ABCC1 p.Arg1142Lys 16230346:132:113
status: NEW139 Therefore, reduced substrate binding appeared to explain, at least in part, the loss of LTC4 transport for the R1138E and K1141E mutants but not the R1138K, R1142E, and R1142K mutants.
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ABCC1 p.Arg1142Lys 16230346:139:169
status: NEW168 In contrast, although [3 H]LTC4 labeling of the R1142E and R1142K mutants was also eliminated by ATP alone, labeling in the orthovanadate-induced ADP trapped (low affinity) state was stronger for these two mutants than for wild-type MRP1.
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ABCC1 p.Arg1142Lys 16230346:168:59
status: NEW169 One possible explanation for this is that the ability of R1142E and R1142K to release LTC4 after ATP hydrolysis might be impaired, which could contribute to their reduced transport activity.
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ABCC1 p.Arg1142Lys 16230346:169:68
status: NEW211 As with the Arg1138 mutants and in contrast to the Lys1141 mutants, our observations with R1142K and R1142E indicated that it is necessary to preserve both the charge and the size of the cationic side chain at position 1142 for full MRP1 transport activity. This may reflect the capacity of Arg to form bidentate hydrogen bonds that Lys cannot.
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ABCC1 p.Arg1142Lys 16230346:211:90
status: NEW227 Wild-type (WT-MRP1) and Arg1142 mutant (R1142E, R1142K) membrane vesicles (50 g of protein) were incubated in transport buffer containing 5 mM MgCl2 for 20 min in the absence (-) or presence (ϩ) of ATP (1 mM) and sodium orthovanadate (1 mM),aloneorincombination,andthenincubatedwith[3 H]LTC4 (200nM,90nCi)forafurther 30 min followed by UV cross-linking, SDS-PAGE, and fluorography. The levels of [3 H]LTC4 labeling in the presence of ATP, and ATP plus orthovanadate, are expressed relative to the labeling in the absence of both agents for each sample and are indicated by the numbers below the film.
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ABCC1 p.Arg1142Lys 16230346:227:48
status: NEW
PMID: 21143116
[PubMed]
He SM et al: "Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1)."
No.
Sentence
Comment
744
The Arg1138Glu and Lys1141Glu mutants, but not the Arg1138Lys, Arg1142Glu, and Arg1142Lys mutants, showed a >50% decrease in binding to [3 H]LTC4.
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ABCC1 p.Arg1142Lys 21143116:744:79
status: NEW