8UC0

Endogenous ligand bound FLVCR1

8UC0 の概要

• エントリーDOI: 10.2210/pdb8uc0/pdb
• EMDBエントリー: 42111
• 分子名称: Heme transporter FLVCR1, CHOLESTEROL HEMISUCCINATE (3 entities in total)
• 機能のキーワード: choline, ethanolamine, membrane transport, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61359.53

構造登録者

Hite, R.K.,Son, Y. (登録日: 2023-09-25, 公開日: 2024-03-27, 最終更新日: 2025-05-28)

主引用文献

Son, Y.,Kenny, T.C.,Khan, A.,Birsoy, K.,Hite, R.K.
Structural basis of lipid head group entry to the Kennedy pathway by FLVCR1.
Nature, 629:710-716, 2024

PubMed Abstract: Phosphatidylcholine and phosphatidylethanolamine, the two most abundant phospholipids in mammalian cells, are synthesized de novo by the Kennedy pathway from choline and ethanolamine, respectively. Despite the essential roles of these lipids, the mechanisms that enable the cellular uptake of choline and ethanolamine remain unknown. Here we show that the protein encoded by FLVCR1, whose mutation leads to the neurodegenerative syndrome posterior column ataxia and retinitis pigmentosa, transports extracellular choline and ethanolamine into cells for phosphorylation by downstream kinases to initiate the Kennedy pathway. Structures of FLVCR1 in the presence of choline and ethanolamine reveal that both metabolites bind to a common binding site comprising aromatic and polar residues. Despite binding to a common site, FLVCR1 interacts in different ways with the larger quaternary amine of choline in and with the primary amine of ethanolamine. Structure-guided mutagenesis identified residues that are crucial for the transport of ethanolamine, but dispensable for choline transport, enabling functional separation of the entry points into the two branches of the Kennedy pathway. Altogether, these studies reveal how FLVCR1 is a high-affinity metabolite transporter that serves as the common origin for phospholipid biosynthesis by two branches of the Kennedy pathway.

PubMed: 38693265
DOI: 10.1038/s41586-024-07374-4

実験手法

ELECTRON MICROSCOPY (2.42 Å)