8Z8Z

Cryo-EM structure of LYCHOS

これはPDB形式変換不可エントリーです。

8Z8Z の概要

• エントリーDOI: 10.2210/pdb8z8z/pdb
• EMDBエントリー: 39851
• 分子名称: Lysosomal cholesterol signaling protein,Fluorescent Protein, 2-acetamido-2-deoxy-beta-D-glucopyranose, [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate, ... (8 entities in total)
• 機能のキーワード: lysosome, gpcr-like, transporter, cholesterol, 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: 263044.10

構造登録者

Xiong, Q.,Zhu, Z.,Li, T.,Zhou, Z.,Chao, Y.,Qu, Q.,Li, D. (登録日: 2024-04-22, 公開日: 2025-01-01, 最終更新日: 2025-02-05)

主引用文献

Xiong, Q.,Zhu, Z.,Li, T.,Li, X.,Zhou, Z.,Chao, Y.,Yang, C.,Feng, S.,Qu, Q.,Li, D.
Molecular architecture of human LYCHOS involved in lysosomal cholesterol signaling.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Lysosomal membrane protein LYCHOS (lysosomal cholesterol signaling) translates cholesterol abundance to mammalian target of rapamycin activation. Here we report the 2.11-Å structure of human LYCHOS, revealing a unique fusion architecture comprising a G-protein-coupled receptor (GPCR)-like domain and a transporter domain that mediates homodimer assembly. The NhaA-fold transporter harbors a previously uncharacterized intramembrane Na pocket. The GPCR-like domain is stabilized, by analogy to canonical GPCRs, in an inactive state through 'tethered antagonism' by a lumenal loop and strong interactions at the cytosol side preventing the hallmark swing of the sixth transmembrane helix seen in active GPCRs. A cholesterol molecule and an associated docosahexaenoic acid (DHA)-phospholipid are entrapped between the transporter and GPCR-like domains, with the DHA-phospholipid occupying a pocket previously implicated in cholesterol sensing, indicating inter-domain coupling via dynamic lipid-protein interactions. Our work provides a high-resolution framework for functional investigations of the understudied LYCHOS protein.

PubMed: 39824977
DOI: 10.1038/s41594-024-01474-5

実験手法

ELECTRON MICROSCOPY (2.11 Å)