ArticleNature structural & molecular biology2022
Structural insights into the lysophospholipid brain uptake mechanism and its inhibition by syncytin-2.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- MFSD2A in health and disease: lysolipid transport, barrier physiology, and translational boundaries.Molecular biomedicine · 2026Review
- Structural insight into sodium-dependent bile acid transport by members of the SLC10 family.Structure (London, England : 1993) · 2026Article
- Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.Nature communications · 2026Article
- In vitro Reconstitution of Syncytin-2 and MFSD2A Reveals their Functional Tethering in Membrane Fusion Initiation.The Journal of membrane biology · 2026Article
- Crystal structure of HERV-K envelope glycoprotein surface subunit.Journal of virology · 2026Article
- Cross-species insights into placental evolution and diseases at the single-cell resolution.Nature communications · 2026Article
- Amino acid and viral binding by the high-affinity Cationic Amino acid Transporter 1 (CAT1) from Mus musculus.Nature communications · 2026Article
- Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B.bioRxiv : the preprint server for biology · 2026Article
- MFSD2A: a molecular nexus linking blood-brain barrier, lipid metabolism, and ischemia-reperfusion injury.Cellular & molecular biology letters · 2025Review
- Structural insights into cationic amino acid transport and viral receptor engagement by CAT1.Nature communications · 2025Article
- MFSD2A in Focus: the Molecular Mechanism of Omega-3 Fatty Acid Transport.Physiology (Bethesda, Md.) · 2025Review
- Human endogenous retrovirus K (HERV-K) envelope structures in pre- and postfusion by cryo-EM.Science advances · 2025Article
- The prefusion structure of the HERV-K (HML-2) Env spike complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake.Nature communications · 2025Article
- Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2.Nature communications · 2025Article
- Molecular basis of Spns1-mediated lysophospholipid transport from the lysosome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Receptor-recognition and antiviral mechanisms of retrovirus-derived human proteins.Nature structural & molecular biology · 2024Article
- Structural basis of Sphingosine-1-phosphate transport via human SPNS2.Cell research · 2024Article
- Molecular basis of Spns2-facilitated sphingosine-1-phosphate transport.Cell research · 2024Article
- Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410.Nature communications · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain development and function require uptake of essential omega-3 fatty acids in the form of lysophosphatidylcholine via major-facilitator superfamily transporter MFSD2A, a potential pharmaceutical target to modulate blood-brain barrier (BBB) permeability. MFSD2A is also the receptor of endogenous retroviral envelope syncytin-2 (SYNC2) in human placenta, where it mediates cell-cell fusion and formation of the maternal-fetal interface. Here, we report a cryo-electron microscopy structure of the human MFSD2A-SYNC2 complex that reveals a large hydrophobic cavity in the transporter C-terminal domain to occlude long aliphatic chains. The transporter architecture suggests an alternating-access transport mechanism for lipid substrates in mammalian MFS transporters. SYNC2 establishes an extensive binding interface with MFSD2A, and a SYNC2-soluble fragment acts as a long-sought-after inhibitor of MFSD2A transport. Our work uncovers molecular mechanisms important to brain and placenta development and function, and SYNC2-mediated inhibition of MFSD2A transport suggests strategies to aid delivery of therapeutic macromolecules across the BBB.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.