ABCB1 p.Arg276Ala
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PMID: 23634976
[PubMed]
Loo TW et al: "A salt bridge in intracellular loop 2 is essential for folding of human p-glycoprotein."
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27
By contrast, none of the Gly mutations in ICL1, -3, or -4 inhibited maturation.10 To test if the charged amino acids Glu256 and Arg276 were important for maturation, we characterized mutants E256A and R276A.
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ABCB1 p.Arg276Ala 23634976:27:201
status: NEW28 Figure 1E shows that E256A or R276A mutations inhibited maturation.
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ABCB1 p.Arg276Ala 23634976:28:30
status: NEW29 While the mature 170 kDa protein was the major product of wild-type P-gp, the immature 150 kDa protein was the major product of mutants E256A and R276A.
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ABCB1 p.Arg276Ala 23634976:29:146
status: NEW31 It was found that the E255A, K271A, K272A, E273A, and E275A mutants were different from the E256A and R276A mutants because they yielded mature 170 kDa P-gp as their major product (Figure 1E).
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ABCB1 p.Arg276Ala 23634976:31:102
status: NEW44 To address this question, we first tested whether it was possible to promote maturation of the E256A or R276A mutant.
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ABCB1 p.Arg276Ala 23634976:44:104
status: NEW45 We previously showed that P-gp was inactive when it was trapped in the ER as a core-glycosylated intermediate.16 Drug substrates (e.g., cyclosporine A) can promote maturation of P-gp processing mutants.17 Mutants E256A and R276A were expressed in HEK293 cells in the presence or absence of 10 bc;M cyclosporine A.
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ABCB1 p.Arg276Ala 23634976:45:223
status: NEW48 The putative Glu256-Arg276 salt bridge was not essential for activity as both the E256A and R276A mutants showed wild-type verapamil-stimulated ATPase activity (Figure S1B of the Supporting Information).
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ABCB1 p.Arg276Ala 23634976:48:92
status: NEW