A SACCHAROMYCES-CEREVISIAE HOMOLOG OF THE HUMAN ADRENOLEUKODYSTROPHY TRANSPORTER IS A HETERODIMER OF 2 HALF ATP-BINDING CASSETTE TRANSPORTERS

The adrenoleukodystrophy protein (ALDP) and the 70-kDa peroxisomal mem brane protein (PMP70) are half ATP-binding cassette (ABC) transporters in the human peroxisome membrane. ALDP and PMP70 share sequence homol ogy and both are implicated in genetic diseases. PXA1 and YKL741 are S accharomyces cerevisiae genes that encode homologs of ALDP and PMP70. Pxa1p, a putative ortholog of ALDP, is involved in peroxisomal beta-ox idation of fatty acids while YKL741 is an open reading frame found by the yeast genome sequencing project. Here we designate YKL741 as PX42 and show that its protein product, Pxa2p, like Pxa1p, is associated wi th peroxisomes but not required for their assembly. Yeast strains carr ying gene disruptions of PXA1, PXA2, or both have similar and, in the case of the latter, nonadditive phenotypes. We also find that the stab ility of Pxa1p, but not Pxa2p, is markedly reduced,in the absence of t he other. Finally, we find that Pxa1p and Pxa2p coimmunoprecipitate. T hese genetic and physical data suggest that Pxa1p and Pxa2p heterodime rize to form a complete peroxisomal ABC transporter involved in fatty acid beta-oxidation. This result predicts the presence of similar hete rodimeric ABC transporters in the mammalian peroxisome membrane.