Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A.

ABSTRACT: Major Facilitator Superfamily Domain containing 2 A (MFSD2A) is a transporter that is highly enriched at the blood-brain and blood-retinal barriers, where it mediates Na⁺-dependent uptake of ω-3 fatty acids in the form of lysolipids into the brain and eyes, respectively. Despite recent structural insights, it remains unclear how this process is initiated, and driven by Na⁺. Here, we perform Molecular Dynamics simulations which demonstrate that substrates enter outward facing MFSD2A from the outer leaflet of the membrane via lateral openings between transmembrane helices 5/8 and 2/11. The substrate headgroup enters first and engages in Na⁺ -bridged interactions with a conserved glutamic acid, while the tail is surrounded by hydrophobic residues. This binding

SUBMITTER: Bergman S 

PROVIDER: S-EPMC10250862 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature