TY - JOUR
T1 - Characterization and analysis of conserved motifs in a peroxisomal ATP-binding cassette transporter
AU - Shani, Noam
AU - Sapag, Amalia
AU - Valle, David
PY - 1996/4/12
Y1 - 1996/4/12
N2 - 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 loopl motifs. We study them by introducing missense mutations in Pxalp, a Saccharomyces cerevisiae ortholog of ALDP, and show that both motifs are important for Pxalp 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 Pxalp is a useful system, for understanding the molecular basis of adrenoleukodystrophy.
AB - 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 loopl motifs. We study them by introducing missense mutations in Pxalp, a Saccharomyces cerevisiae ortholog of ALDP, and show that both motifs are important for Pxalp 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 Pxalp is a useful system, for understanding the molecular basis of adrenoleukodystrophy.
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U2 - 10.1074/jbc.271.15.8725
DO - 10.1074/jbc.271.15.8725
M3 - Article
C2 - 8621506
AN - SCOPUS:0029883155
SN - 0021-9258
VL - 271
SP - 8725
EP - 8730
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 15
ER -