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Structural insights into the lysophospholipid brain uptake mechanism and its inhibition by syncytin-2.
| dc.rights.license | open | en_US |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | MARTINEZ-MOLLEDO, Maria | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | NJI, Emmanuel | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | REYES, Nicolas | |
| dc.date.accessioned | 2024-10-01T09:35:23Z | |
| dc.date.available | 2024-10-01T09:35:23Z | |
| dc.date.issued | 2022-06-01 | |
| dc.identifier.issn | 1545-9985 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/202084 | |
| dc.description.abstractEn | 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. | |
| dc.language.iso | EN | en_US |
| dc.subject.en | Animals | |
| dc.subject.en | Brain | |
| dc.subject.en | Cryoelectron Microscopy | |
| dc.subject.en | Female | |
| dc.subject.en | Humans | |
| dc.subject.en | Lysophosphatidylcholines | |
| dc.subject.en | Mammals | |
| dc.subject.en | Membrane Transport Proteins | |
| dc.subject.en | Pregnancy | |
| dc.subject.en | Pregnancy Proteins | |
| dc.subject.en | Symporters | |
| dc.title.en | Structural insights into the lysophospholipid brain uptake mechanism and its inhibition by syncytin-2. | |
| dc.title.alternative | Nat Struct Mol Biol | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1038/s41594-022-00786-8 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Microbiologie et Parasitologie | en_US |
| dc.identifier.pubmed | 35710838 | en_US |
| bordeaux.journal | Nature Structural and Molecular Biology | en_US |
| bordeaux.page | 604-612 | en_US |
| bordeaux.volume | 29 | en_US |
| bordeaux.hal.laboratories | MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234 | en_US |
| bordeaux.issue | 6 | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | pubmed | |
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| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | true | |
| workflow.import.source | pubmed | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature%20Structural%20and%20Molecular%20Biology&rft.date=2022-06-01&rft.volume=29&rft.issue=6&rft.spage=604-612&rft.epage=604-612&rft.eissn=1545-9985&rft.issn=1545-9985&rft.au=MARTINEZ-MOLLEDO,%20Maria&NJI,%20Emmanuel&REYES,%20Nicolas&rft.genre=article |
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