![]() Cryo-EM structure of human lysosomal cobalamin exporter ABCD4. Conformational dynamics of the ABC transporter McjD seen by single-molecule FRET. Conformation space of a heterodimeric ABC exporter under turnover conditions. Functional non-equivalence of ATP-binding cassette signature motifs in the transporter associated with antigen processing (TAP). Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. Crystal structures of a polypeptide processing and secretion transporter. ECF-type ATP-binding cassette transporters. Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state. Structural diversity of ABC transporters. Structural insight into substrate and inhibitor discrimination by human P-glycoprotein. Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Effects of a detergent micelle environment on P-glycoprotein (ABCB1)–ligand interactions. BacA, an ABC transporter involved in maintenance of chronic murine infections with Mycobacterium tuberculosis. Functional and structural characterization of an ECF-type ABC transporter for vitamin B 12. Cysteine-mediated decyanation of vitamin B 12 by the predicted membrane transporter BtuM. Structure of AMP-PNP-bound vitamin B 12 transporter BtuCD-F. Vitamin B 12 metabolism in Mycobacterium tuberculosis. ![]() A vitamin B 12 transporter in Mycobacterium tuberculosis. 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, 9, 10, 11. 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 3, which enables the protein to transport the unrelated hydrophilic compounds bleomycin and cobalamin. 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. 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. Mtb does not encode any characterized cobalamin transporter 4, 5, 6 however, the gene rv1819c was found to be essential for uptake of cobalamin 1. Although Mtb can synthesize vitamin B 12 (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis 2. Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis 1, 2, 3.
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