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Targeting, Import, and Dimerization of a Mammalian Mitochondrial ATP Binding Cassette (ABC) Transporter, ABCB10 (ABC-me)
ATP binding cassette (ABC) transporters are a diverse superfamily of energy-dependent membrane translocases. Although responsible for the majority of transmembrane transport in bacteria, they are relatively uncommon in eukaryotic mitochondria. Organellar trafficking and import, in addition to quater...
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Published in: | The Journal of biological chemistry 2004-10, Vol.279 (41), p.42954-42963 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | ATP binding cassette (ABC) transporters are a diverse superfamily of energy-dependent membrane translocases. Although responsible
for the majority of transmembrane transport in bacteria, they are relatively uncommon in eukaryotic mitochondria. Organellar
trafficking and import, in addition to quaternary structure assembly, of mitochondrial ABC transporters is poorly understood
and may offer explanations for the paucity of their diversity. Here we examine these processes in ABCB10 (ABC-me), a mitochondrial
inner membrane erythroid transporter involved in heme biosynthesis. We report that ABCB10 possesses an unusually long 105-amino
acid mitochondrial targeting presequence (mTP). The central subdomain of the mTP (amino acids (aa) 36â70) is sufficient for
mitochondrial import of enhanced green fluorescent protein. The N-terminal subdomain (aa 1â35) of the mTP, although not necessary
for the trafficking of ABCB10 to mitochondria, participates in the proper import of the molecule into the inner membrane.
We performed a series of amino acid mutations aimed at changing specific properties of the mTP. The mTP requires neither arginine
residues nor predictable α-helices for efficient mitochondrial targeting. Disruption of its hydrophobic character by the mutation
L46Q/I47Q, however, greatly diminishes its efficacy. This mutation can be rescued by cryptic downstream (aa 106â715) mitochondrial
targeting signals, highlighting the redundancy of this protein's targeting qualities. Mass spectrometry analysis of chemically
cross-linked, immunoprecipitated ABCB10 indicates that ABCB10 embedded in the mitochondrial inner membrane homodimerizes and
homo-oligomerizes. A deletion mutant of ABCB10 that lacks its mTP efficiently targets to the endoplasmic reticulum. Quaternary
structure assembly of ABCB10 in the ER appears to be similar to that in the mitochondria. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M405040200 |