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A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds
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Number of Authors: 82020 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 580, no 7803, p. 409-412Article in journal (Refereed) Published
Abstract [en]

Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis(1-3). Although Mtb can synthesize vitamin B-12 (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis(2). Mtb does not encode any characterized cobalamin transporter(4-6); however, the gene rv1819c was found to be essential for uptake of cobalamin(1). This result is difficult to reconcile with the original annotation of Rv1819c as a protein implicated in the transport of antimicrobial peptides such as bleomycin(7). In addition, uptake of cobalamin seems inconsistent with the amino acid sequence, which suggests that Rv1819c has a bacterial ATP-binding cassette (ABC)-exporter fold(1). Here, we present structures of Rv1819c, which reveal that the protein indeed contains the ABC-exporter fold, as well as a large water-filled cavity of about 7,700 angstrom(3), which enables the protein to transport the unrelated hydrophilic compounds bleomycin and cobalamin. On the basis of these structures, we propose that Rv1819c is a multi-solute transporter for hydrophilic molecules, analogous to the multidrug exporters of the ABC transporter family, which pump out structurally diverse hydrophobic compounds from cells(8-11). Analysis of cryo-electron microscopy structures of the Mycobacterium tuberculosis ABC transporter Rv1819c suggests that it is a multi-solute transporter for hydrophilic molecules.

Place, publisher, year, edition, pages
2020. Vol. 580, no 7803, p. 409-412
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Biological Sciences
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URN: urn:nbn:se:su:diva-181134DOI: 10.1038/s41586-020-2072-8ISI: 000530151300036PubMedID: 32296172OAI: oai:DiVA.org:su-181134DiVA, id: diva2:1431303
Available from: 2020-05-19 Created: 2020-05-19 Last updated: 2022-02-26Bibliographically approved

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Nijland, M.Karyolaimos, Alexandrosde Gier, Jan WillemGuskov, A.

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