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dc.contributor.authorGraf, Solomon A.  Concept link
dc.contributor.authorHaigh, Sarah E.  Concept link
dc.contributor.authorCorson, Erica D.  Concept link
dc.contributor.authorShirihai, Orian S.  Concept link
dc.date.accessioned2009-04-24T18:23:31Z
dc.date.available2009-04-24T18:23:31Z
dc.date.issued2004-06-23
dc.identifier.citationJournal of Biological Chemistry 279 (2004): 42954-42963en
dc.identifier.urihttps://hdl.handle.net/1912/2807
dc.descriptionAuthor Posting. © American Society for Biochemistry and Molecular Biology, 2004. This article is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 279 (2004): 42954-42963, doi:10.1074/jbc.M405040200.en
dc.description.abstractATP 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) 36–70) is sufficient for mitochondrial import of enhanced green fluorescent protein. The N-terminal subdomain (aa 1–35) 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 {alpha}-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 106–715) 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.en
dc.description.sponsorshipThis work was supported by National Institutes of Health Grants R01HL071629, P41RR001395, and P01HL032262.en
dc.format.mimetypeapplication/pdf
dc.language.isoen_USen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.relation.urihttps://doi.org/10.1074/jbc.M405040200
dc.titleTargeting, import, and dimerization of a mammalian mitochondrial ATP binding cassette (ABC) transporter, ABCB10 (ABC-me)en
dc.typeArticleen
dc.identifier.doi10.1074/jbc.M405040200


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