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A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds

Rempel, S., Gati, C., Nijland, M., Thangaratnarajah, C., Karyolaimos, A., Gier, J-W. L. D., Guskov, A. & Slotboom, D., 25-Mar-2020, In : Nature. 580, 7803, p. 409-412 4 p.

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  • A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds

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DOI

Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis1,2,3. Although Mtb can synthesize vitamin B12 (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis2. Mtb does not encode any characterized cobalamin transporter4,5,6; however, the gene rv1819c was found to be essential for uptake of cobalamin1. This result is difficult to reconcile with the original annotation of Rv1819c as a protein implicated in the transport of antimicrobial peptides such as bleomycin7. In addition, uptake of cobalamin seems inconsistent with the amino acid sequence, which suggests that Rv1819c has a bacterial ATP-binding cassette (ABC)-exporter fold1. 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 Å3, 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 cells8,9,10,11.
Original languageEnglish
Pages (from-to)409-412
Number of pages4
JournalNature
Volume580
Issue number7803
Publication statusPublished - 25-Mar-2020
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