6TQE

The structure of ABC transporter Rv1819c without addition of substrate

Summary for 6TQE

• Entry DOI: 10.2210/pdb6tqe/pdb
• EMDB information: 10549
• Descriptor: ABC transporter ATP-binding protein/permease, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION (3 entities in total)
• Functional Keywords: cobalamin, vitamin b12, abc transporter, exporter fold, import, tuberculosis, transport protein
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 145906.97

Authors

Rempel, S.,Gati, C.,Slotboom, D.J.,Guskov, A. (deposition date: 2019-12-16, release date: 2020-04-01, Last modification date: 2024-05-22)

Primary citation

Rempel, S.,Gati, C.,Nijland, M.,Thangaratnarajah, C.,Karyolaimos, A.,de Gier, J.W.,Guskov, A.,Slotboom, D.J.
A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds.
Nature, 580:409-412, 2020

PubMed Abstract: Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis. Although Mtb can synthesize vitamin B (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis. Mtb does not encode any characterized cobalamin transporter; however, the gene rv1819c was found to be essential for uptake of cobalamin. 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. 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. 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, 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.

PubMed: 32296172
DOI: 10.1038/s41586-020-2072-8

Experimental method

ELECTRON MICROSCOPY (4.3 Å)