1. A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds
- Author
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Rempel, S., Gati, C., Nijland, M., Thangaratnarajah, C., Karyolaimos, A., de Gier, J. W., and Guskov, A.
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Carrier proteins -- Influence -- Analysis -- Chemical properties ,Vitamin B12 -- Analysis -- Chemical properties ,ATP synthesis -- Analysis -- Chemical properties ,Mycobacterium tuberculosis -- Structure -- Analysis -- Chemical properties ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis.sup.1-3. Although Mtb can synthesize vitamin B.sub.12 (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis.sup.2. Mtb does not encode any characterized cobalamin transporter.sup.4-6; however, the gene rv1819c was found to be essential for uptake of cobalamin.sup.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.sup.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.sup.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 Å.sup.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.sup.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., Author(s): S. Rempel [sup.1] [sup.7] , C. Gati [sup.2] [sup.3] , M. Nijland [sup.1] , C. Thangaratnarajah [sup.1] , A. Karyolaimos [sup.4] , J. W. de Gier [sup.4] , A. [...]
- Published
- 2020
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