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-Structure paper
Title | A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds. |
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Journal, issue, pages | Nature, Vol. 580, Issue 7803, Page 409-412, Year 2020 |
Publish date | Mar 25, 2020 |
Authors | S Rempel / C Gati / M Nijland / C Thangaratnarajah / A Karyolaimos / J W de Gier / A Guskov / D J Slotboom / |
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 ...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. |
External links | Nature / PubMed:32296172 |
Methods | EM (single particle) |
Resolution | 3.5 - 4.3 Å |
Structure data | EMDB-10549, PDB-6tqe: EMDB-10550, PDB-6tqf: |
Chemicals | ChemComp-ATP: ChemComp-MG: ChemComp-LMT: ChemComp-ANP: |
Source |
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Keywords | TRANSPORT PROTEIN / cobalamin / vitamin B12 / ABC transporter / exporter fold / import / tuberculosis |