ABCB1 p.Leu70Gly
| Predicted by SNAP2: | A: D (53%), C: N (61%), D: D (75%), E: D (71%), F: N (78%), G: D (71%), H: D (66%), I: N (97%), K: D (71%), M: N (72%), N: D (71%), P: D (75%), Q: D (63%), R: D (66%), S: D (63%), T: N (72%), V: N (87%), W: D (63%), Y: N (53%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Characterization and analysis of conserved motifs ... J Biol Chem. 1996 Apr 12;271(15):8725-30. Shani N, Sapag A, Valle D
Characterization and analysis of conserved motifs in a peroxisomal ATP-binding cassette transporter.
J Biol Chem. 1996 Apr 12;271(15):8725-30., [PMID:8621506]
Abstract [show]
The adrenoleukodystrophy protein (ALDP) and the 70-kDa peroxisomal membrane protein are half ATP-binding cassette (ABC) transporters in the human peroxisome membrane. Both are implicated in genetic disorders of peroxisome biogenesis and function. Proteins homologous to ALDP and the 70-kDa peroxisomal membrane protein have been discovered in other eukaryotic organisms and form a growing group of peroxisomal half ABC transporters. Amino acid sequence alignment of these and other ABC transporters reveals several protein motifs that are highly conserved both in sequence and location. Here we characterize two of these, designated the EAA-like and the loop1 motifs. We study them by introducing missense mutations in Pxa1p, a Saccharomyces cerevisiae ortholog of ALDP, and show that both motifs are important for Pxa1p function. Interestingly, missense mutations in corresponding amino acids in ALDP cause adrenoleukodystrophy in humans. We conclude that these motifs are important for ABC transporter function and that the yeast protein Pxa1p is a useful system for understanding the molecular basis of adrenoleukodystrophy.
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No. Sentence Comment
98 We also changed a nonconserved amino acid near the loop1 motif (L70) to glycine because in previous work we suggested that this residue might play a role in fatty acid binding (11) Analysis of the loop1 Protein Motif-Alterations of the conserved loop1 arginine have an effect on Pxa1p function (Fig. 6); the R108L mutation has a null phenotype, as measured by growth on oleic acid and the beta-oxidation assay; R108K has an intermediate phenotype in both assays (approximately 50% of wild type), whereas the growth phenotype of L70G was indistinguishable from wild type (Fig. 6) (beta-oxidation not performed).
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ABCB1 p.Leu70Gly 8621506:98:528
status: NEW112 A, phenotypes of pxa1::LEU2 knockout (ko) yeast expressing (from left to right): wild type (wt), L70G, R108L, and R108K alleles of PXA1 or vector alone. 10-fold dilutions (top to bottom) of the different cells were inoculated on medium containing 0.1% oleic acid as a sole carbon source.
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ABCB1 p.Leu70Gly 8621506:112:97
status: NEW