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TitleA mycobacterial ABC transporter mediates the uptake of hydrophilic compounds.
Journal, issue, pagesNature, Vol. 580, Issue 7803, Page 409-412, Year 2020
Publish dateMar 25, 2020
AuthorsS Rempel / C Gati / M Nijland / C Thangaratnarajah / A Karyolaimos / J W de Gier / A Guskov / D J Slotboom /
PubMed AbstractMycobacterium 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 linksNature / PubMed:32296172
MethodsEM (single particle)
Resolution3.5 - 4.3 Å
Structure data

EMDB-10549, PDB-6tqe:
The structure of ABC transporter Rv1819c without addition of substrate
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-10550, PDB-6tqf:
The structure of ABC transporter Rv1819c in AMP-PNP bound state
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-MG:
Unknown entry

ChemComp-LMT:
DODECYL-BETA-D-MALTOSIDE / detergent*YM

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • mycobacterium tuberculosis (bacteria)
KeywordsTRANSPORT PROTEIN / cobalamin / vitamin B12 / ABC transporter / exporter fold / import / tuberculosis

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