ABCMdb

ABCB1 p.Ala266Cys

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Publications

PMID: 18708637 [PubMed] Loo TW et al: "Processing mutations disrupt interactions between the nucleotide binding and transmembrane domains of P-glycoprotein and the cystic fibrosis transmembrane conductance regulator (CFTR)."

No. Sentence Comment

107 The locations of positions equivalent to cysteines S473C and R905C in the other half of P-gp (A266C/F1086C) are indicated. Login to comment
151 Because no cross-linking studies have identified cysteines that could be cross-linked at the TMD1-NBD2 interface, we constructed a series of double cysteine mutants between a cysteine in TMD1 (A266C or F267C) and another in NBD2 (R1085C, F1086C, Y1087C or D1088C) that would be equivalent to L443C(NBD1) and S909C(TMD2), respectively, in each half of P-gp. Login to comment
164 A, membranes prepared from cells expressing mutant A266C/F1086C were treated with (ϩ) or without (-) 1 mM copper phenanthroline (CuP) for 15 min at 0 °C. Membranes were also treated with drug substrates or ATP plus vanadate as described in the legend to Fig. 4. Login to comment

PMID: 21182301 [PubMed] Loo TW et al: "The W232R suppressor mutation promotes maturation of a truncation mutant lacking both nucleotide-binding domains and restores interdomain assembly and activity of P-glycoprotein processing mutants."

No. Sentence Comment

164 Accordingly, we introduced the W232R mutation into mutant A266C/F1086C/L1260A. Login to comment
166 Figure 3C shows that the W232R mutation promoted maturation of the mutant A266C/F1086C/L1260A (lane 3) and that only the mature protein was cross-linked (lane 4). Login to comment
188 Membranes were also prepared from cells expressing the L1260A processing mutant ( W232R containing cysteines in TMD1 and NBD2 (A266C/F1086C) (C). Login to comment

PMID: 23634976 [PubMed] Loo TW et al: "A salt bridge in intracellular loop 2 is essential for folding of human p-glycoprotein."

No. Sentence Comment

13 ICL2 appears to play a key role in coupling NBD1-TMD2 interactions because cysteines introduced into ICL2 (A266C) and NBD2 (F1086C) could be cross-linked and the F1086C change abolished activity.13 While both structures predict that residues 261-267 form an interhelical loop (IH2) (forms the ball portion of the ball-and-socket ICL2-NBD connection), adjacent amino acids were predicted to adopt loop or b1;-helical structures in the mouse or C. elegans structures, respectively. Login to comment

PMID: 23733192 [PubMed] Loo TW et al: "Human P-glycoprotein contains a greasy ball-and-socket joint at the second transmission interface."

No. Sentence Comment

56 IH2 appears to be particularly important because we showed that a cysteine introduced into IH2 (A266C) could be directly cross-linked to a cysteine in NBD2 (F1086C) but the mutant was inactive (21). Login to comment
62 Because mutant A266C/F1086C was inactive, we characterized the Ala-266/ Phe-1086 interface to determine its role in the transport cycle. Login to comment
109 In a previous study, we provided biochemical evidence that Ala-266 was indeed close to Phe-1086 in NBD2 because mutant A266C/F1086C showed robust cross-linking even when treated with oxidant at 0 &#b0;C to slow molecular motion (21). Login to comment
110 The Ala-266/Phe-1086 contact point appeared to be critical for function because mutant A266C/F1086C was inactive (21). Login to comment
117 IH2 Mediates TMD/NBD Coupling in the P-gp Drug Pump 20328 JOURNAL OF BIOLOGICAL CHEMISTRY VOLUME 288ߦNUMBER 28ߦJULY 12, 2013 To determine whether one or both cysteine mutations in mutant A266C/F1086C inhibited activity, mutants were constructed in a Cys-less background that contained only Cys-266 or Cys-1086. Login to comment
138 A and B, structures of P-gp in the open (A) (17) or closed (B) (24) conformations are shown. C, histidine-tagged Cys-less P-gp or mutants A266C/F1086C, A266C, and F1086C (in Cys-less background) as well as wild-type P-gp and mutant F1086A ( in wild-type background) were isolated, and ATPase activities were measured in the presence of verapamil. Login to comment