7OIX
Structure of thermostable human MFSD2A in complex with thermostable human Sync2
Summary for 7OIX
| Entry DOI | 10.2210/pdb7oix/pdb |
| EMDB information | 12935 |
| Descriptor | Syncytin-2, Isoform 2 of Sodium-dependent lysophosphatidylcholine symporter 1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | human membrane protein, mfs transporter, human endogenous retroviral protein, syncytin, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 121405.99 |
| Authors | Martinez-Molledo, M.,Reyes, N. (deposition date: 2021-05-12, release date: 2022-06-01, Last modification date: 2025-12-24) |
| Primary citation | Martinez-Molledo, M.,Nji, E.,Reyes, N. Structural insights into the lysophospholipid brain uptake mechanism and its inhibition by syncytin-2. Nat.Struct.Mol.Biol., 29:604-612, 2022 Cited by PubMed 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. PubMed: 35710838DOI: 10.1038/s41594-022-00786-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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