7OIX

Structure of thermostable human MFSD2A in complex with thermostable human Sync2

7OIX の概要

• エントリーDOI: 10.2210/pdb7oix/pdb
• EMDBエントリー: 12935
• 分子名称: 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)
• 機能のキーワード: human membrane protein, mfs transporter, human endogenous retroviral protein, syncytin, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 121405.99

構造登録者

Martinez-Molledo, M.,Reyes, N. (登録日: 2021-05-12, 公開日: 2022-06-01, 最終更新日: 2025-12-24)

主引用文献

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

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: 35710838
DOI: 10.1038/s41594-022-00786-8

実験手法

ELECTRON MICROSCOPY (3.6 Å)