8D2U

Zebrafish MFSD2A isoform B in inward open ligand 1A conformation

Summary for 8D2U

• Entry DOI: 10.2210/pdb8d2u/pdb
• Related: 8D2S 8D2T 8D2V 8D2W 8D2X
• EMDB information: 27148 27149 27150 27151 27152 27153
• Descriptor: Sodium-dependent lysophosphatidylcholine symporter 1-B, FAB light chain, FAB heavy chain, ... (7 entities in total)
• Functional Keywords: omega-3 fatty acid, lipid transport, membrane protein, fab
• Biological source: Danio rerio (zebrafish); More
• Total number of polymer chains: 3
• Total formula weight: 106638.41

Authors

Nguyen, C.,Lei, H.T.,Lai, L.T.F.,Gallentino, M.J.,Mu, X.,Matthies, D.,Gonen, T. (deposition date: 2022-05-30, release date: 2023-05-10, Last modification date: 2023-05-24)

Primary citation

Nguyen, C.,Lei, H.T.,Lai, L.T.F.,Gallenito, M.J.,Mu, X.,Matthies, D.,Gonen, T.
Lipid flipping in the omega-3 fatty-acid transporter.
Nat Commun, 14:2571-2571, 2023

PubMed Abstract: Mfsd2a is the transporter for docosahexaenoic acid (DHA), an omega-3 fatty acid, across the blood brain barrier (BBB). Defects in Mfsd2a are linked to ailments from behavioral and motor dysfunctions to microcephaly. Mfsd2a transports long-chain unsaturated fatty-acids, including DHA and α-linolenic acid (ALA), that are attached to the zwitterionic lysophosphatidylcholine (LPC) headgroup. Even with the recently determined structures of Mfsd2a, the molecular details of how this transporter performs the energetically unfavorable task of translocating and flipping lysolipids across the lipid bilayer remains unclear. Here, we report five single-particle cryo-EM structures of Danio rerio Mfsd2a (drMfsd2a): in the inward-open conformation in the ligand-free state and displaying lipid-like densities modeled as ALA-LPC at four distinct positions. These Mfsd2a snapshots detail the flipping mechanism for lipid-LPC from outer to inner membrane leaflet and release for membrane integration on the cytoplasmic side. These results also map Mfsd2a mutants that disrupt lipid-LPC transport and are associated with disease.

PubMed: 37156797
DOI: 10.1038/s41467-023-37702-7

Experimental method

ELECTRON MICROSCOPY (3.3 Å)