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

Summary for 8PNL

• Entry DOI: 10.2210/pdb8pnl/pdb
• Descriptor: Putative triacylglyceride transporter, Nb_H2 (2 entities in total)
• Functional Keywords: major facilitator superfamily transporter, nanobody, outward-open conformation, triacylglyceride extraction, transport protein
• Biological source: Mycolicibacterium hassiacum DSM 44199; More
• Total number of polymer chains: 4
• Total formula weight: 140233.03

Authors

Remm, S.,Schoeppe, J.,Hutter, C.A.J.,Gonda, I.,Seeger, M.A. (deposition date: 2023-06-30, release date: 2023-10-18, Last modification date: 2023-10-25)

Primary citation

Remm, S.,De Vecchis, D.,Schoppe, J.,Hutter, C.A.J.,Gonda, I.,Hohl, M.,Newstead, S.,Schafer, L.V.,Seeger, M.A.
Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410.
Nat Commun, 14:6449-6449, 2023

PubMed Abstract: 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.

PubMed: 37833269
DOI: 10.1038/s41467-023-42073-0

Experimental method

X-RAY DIFFRACTION (2.7 Å)