- PDB-9j3z: Cryo-EM structure of lysosome cholesterol sencing protein in L state -
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基本情報
登録情報
データベース: PDB / ID: 9j3z
タイトル
Cryo-EM structure of lysosome cholesterol sencing protein in L state
要素
Lysosomal cholesterol signaling protein,G protein-coupled receptor 155 fusion protein
キーワード
LIPID BINDING PROTEIN
機能・相同性
機能・相同性情報
cellular response to cholesterol / cholesterol binding / negative regulation of BMP signaling pathway / positive regulation of TORC1 signaling / cellular response to amino acid starvation / transmembrane transport / cognition / intracellular signal transduction / lysosomal membrane / extracellular exosome 類似検索 - 分子機能
Integral membrane protein GPR155, DEP domain / Membrane transport protein / Membrane transport protein / : / Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) / DEP domain profile. / Domain found in Dishevelled, Egl-10, and Pleckstrin / DEP domain / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性
Chem-POV / G protein-coupled receptor 155 / Lysosomal cholesterol signaling protein 類似検索 - 構成要素
ジャーナル: Nat Commun / 年: 2025 タイトル: Structural basis for cholesterol sensing of LYCHOS and its interaction with indoxyl sulfate. 著者: Zhenhua Wang / Jingjing He / Yufan Yang / Yonglin He / Hongwu Qian / 要旨: The lysosome serves as an essential nutrient-sensing hub within the cell, where the mechanistic target of rapamycin complex 1 (mTORC1) is activated. Lysosomal cholesterol signaling (LYCHOS), a ...The lysosome serves as an essential nutrient-sensing hub within the cell, where the mechanistic target of rapamycin complex 1 (mTORC1) is activated. Lysosomal cholesterol signaling (LYCHOS), a lysosome membrane protein, has been identified as a cholesterol sensor that couples cholesterol concentration to mTORC1 activation. However, the molecular basis is unknown. Here, we determine the cryo-electron microscopy (cryo-EM) structure of human LYCHOS at a resolution of 3.1 Å, revealing a cholesterol-like density at the interface between the permease and G-protein coupled receptor (GPCR) domains. Advanced 3D classification reveals two distinct states of LYCHOS. Comparative structural analysis between these two states demonstrated a cholesterol-related movement of GPCR domain relative to permease domain, providing structural insights into how LYCHOS senses lysosomal cholesterol levels. Additionally, we identify indoxyl sulfate (IS) as a binding ligand to the permease domain, confirmed by the LYCHOS-IS complex structure. Overall, our study provides a foundation and indicates additional directions for further investigation of the essential role of LYCHOS in the mTORC1 signaling pathway.
履歴
登録
2024年8月8日
登録サイト: PDBJ / 処理サイト: PDBJ
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2025年4月2日
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2025年4月2日
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