+検索条件
-Structure paper
タイトル | Structural insights into the lysophospholipid brain uptake mechanism and its inhibition by syncytin-2. |
---|---|
ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 29, Issue 6, Page 604-612, Year 2022 |
掲載日 | 2022年6月16日 |
著者 | Maria Martinez-Molledo / Emmanuel Nji / Nicolas Reyes / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:35710838 |
手法 | EM (単粒子) |
解像度 | 3.6 Å |
構造データ | EMDB-12935, PDB-7oix: |
化合物 | ChemComp-NAG: |
由来 |
|
キーワード | MEMBRANE PROTEIN (膜タンパク質) / human membrane protein (膜タンパク質) / MFS transporter / human endogenous retroviral protein / syncytin |