6tqf
The structure of ABC transporter Rv1819c in AMP-PNP bound state
Structural highlights
FunctionBACA_MYCTU Multi-solute ABC transporter that mediates uptake of unrelated hydrophilic compounds (PubMed:32296172). Can transport vitamin B12 and related corrinoids, and antimicrobial peptides such as bleomycin (PubMed:18996991, PubMed:23407640, PubMed:32296172). Transmembrane domains (TMD) form a pore in the membrane and the ATP-binding domain (NBD) is responsible for energy generation (PubMed:32296172). Contributes to maintenance of chronic infections (PubMed:18996991).[1] [2] [3] Publication Abstract from PubMedMycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis(1-3). Although Mtb can synthesize vitamin B12 (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis(2). Mtb does not encode any characterized cobalamin transporter(4-6); however, the gene rv1819c was found to be essential for uptake of cobalamin(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). 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). 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 A(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(8-11). A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds.,Rempel S, Gati C, Nijland M, Thangaratnarajah C, Karyolaimos A, de Gier JW, Guskov A, Slotboom DJ Nature. 2020 Apr;580(7803):409-412. doi: 10.1038/s41586-020-2072-8. Epub 2020 Mar, 25. PMID:32296172[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
