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TitleStructural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 6449, Year 2023
Publish dateOct 13, 2023
AuthorsSille Remm / Dario De Vecchis / Jendrik Schöppe / Cedric A J Hutter / Imre Gonda / Michael Hohl / Simon Newstead / Lars V Schäfer / Markus A Seeger /
PubMed AbstractMycobacterium tuberculosis is protected from antibiotic therapy by a multi-layered hydrophobic cell envelope. Major facilitator superfamily (MFS) transporter Rv1410 and the periplasmic lipoprotein ...Mycobacterium tuberculosis is protected from antibiotic therapy by a multi-layered hydrophobic cell envelope. Major facilitator superfamily (MFS) transporter Rv1410 and the periplasmic lipoprotein LprG are involved in transport of triacylglycerides (TAGs) that seal the mycomembrane. Here, we report a 2.7 Å structure of a mycobacterial Rv1410 homologue, which adopts an outward-facing conformation and exhibits unusual transmembrane helix 11 and 12 extensions that protrude ~20 Å into the periplasm. A small, very hydrophobic cavity suitable for lipid transport is constricted by a functionally important ion-lock likely involved in proton coupling. Combining mutational analyses and MD simulations, we propose that TAGs are extracted from the core of the inner membrane into the central cavity via lateral clefts present in the inward-facing conformation. The functional role of the periplasmic helix extensions is to channel the extracted TAG into the lipid binding pocket of LprG.
External linksNat Commun / PubMed:37833269 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.7 - 3.99 Å
Structure data

EMDB-17787: 4.0 angstrom map of outward-facing MFS transporter MHAS2168, a homologue of M. tuberculosis Rv1410, in complex with a megabody
Method: EM (single particle) / Resolution: 3.99 Å

PDB-8pnl:
Outward-open conformation of a Major Facilitator Superfamily (MFS) transporter MHAS2168, a homologue of Rv1410 from M. tuberculosis, in complex with an alpaca nanobody
Method: X-RAY DIFFRACTION / Resolution: 2.7 Å

Source
  • mycolicibacterium hassiacum dsm 44199 (bacteria)
  • vicugna pacos (alpaca)
KeywordsTRANSPORT PROTEIN / Major Facilitator Superfamily transporter / Nanobody / Outward-open conformation / Triacylglyceride extraction

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