8pnl
From Proteopedia
Outward-open conformation of a Major Facilitator Superfamily (MFS) transporter MHAS2168, a homologue of Rv1410 from M. tuberculosis, in complex with an alpaca nanobody
Structural highlights
FunctionMFS55_MYCHD In association with lipoprotein LprG transports triacylglycerides (TAG) across the inner cell membrane, probably transfering them to lipoprotein LprG in the periplasm (PubMed:37833269). TAG probably regulates lipid metabolism and growth regulation and plays a structural role in the outer membrane (Probable). Mutagenesis and molecular modeling suggests TAG (and maybe other lipids) enters the central cavity of the P55 transporter from within the cell inner membrane via clefts on the cytoplasmic face of P55 between TM5-TM8 and TM2-TM11 (Probable) (PubMed:37833269). From there the lipid is probably transferred to the hydrophobic cavity of LprG (Probable) (PubMed:37833269). The lprG-MHAS_02167/C731_2107 operon complements the vancomycin sensitivity of an M.smegmatis knockout of the same operon (PubMed:37833269). Probably required with LprG for normal surface localization of lipoarabinomannan (LAM).[1] [2] Publication Abstract from PubMedMycobacterium 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 A structure of a mycobacterial Rv1410 homologue, which adopts an outward-facing conformation and exhibits unusual transmembrane helix 11 and 12 extensions that protrude ~20 A 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. Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410.,Remm S, De Vecchis D, Schoppe J, Hutter CAJ, Gonda I, Hohl M, Newstead S, Schafer LV, Seeger MA Nat Commun. 2023 Oct 13;14(1):6449. doi: 10.1038/s41467-023-42073-0. PMID:37833269[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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