EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural insights into cholesterol sensing by the LYCHOS-mTORC1 pathway.
ジャーナル・号・ページ	Nat Commun, Vol. 16, Issue 1, Page 6792, Year 2025
掲載日	2025年7月23日
著者	Shang Yu / Jin-Hui Ding / Jia-le Wang / Weize Wang / Peng Zuo / Ao Yang / Zonglin Dai / Yuxin Yin / Jin-Peng Sun / Ling Liang /
PubMed 要旨	The lysosomal cholesterol sensor LYCHOS regulates mTORC1 signaling by coupling cholesterol sensing to GATOR1-Rag GTPase modulation, yet its structural mechanisms remain unclear. Here we report six ...The lysosomal cholesterol sensor LYCHOS regulates mTORC1 signaling by coupling cholesterol sensing to GATOR1-Rag GTPase modulation, yet its structural mechanisms remain unclear. Here we report six cryo-electron microscopy structures of human LYCHOS, depicting five distinct states. These are categorized into a contracted state when complexed with a sufficient amount of the cholesterol analogue cholesteryl hemisuccinate (CHS), and an expanded state when CHS is deficient. The structure forms a homodimer, within each monomer the transmembrane region is divided into a permease-like domain (PLD) and a GPCR-like domain (GLD) with two clearly defined adjacent cholesterol binding sites between them. Cholesterol binding induces a translation of GLD towards PLD and exposes the cytosolic extension of transmembrane 15, which interacts with GATOR1. Our results elucidate the structural mechanism of cholesterol sensing by the mTORC1 pathway, providing a structural basis for developing inhibitors that selectively target mTORC1 pathway by blocking LYCHOS in its expanded state.
リンク	Nat Commun / PubMed:40702016 / PubMed Central
手法	EM (単粒子)
解像度	2.73 - 4.49 Å
構造データ	61311 9jbe EMDB-61311, PDB-9jbe: Cryo-EM structure of the human LYCHOS in complex with cholesterol and cholesteryl hemisuccinate in the contracted state 手法: EM (単粒子) / 解像度: 3.31 Å 61312 9jbf EMDB-61312, PDB-9jbf: Cryo-EM structure of the human LYCHOS Y57A mutant in complex with cholesteryl hemisuccinate in the contracted state 手法: EM (単粒子) / 解像度: 3.21 Å 61313 9jbg EMDB-61313, PDB-9jbg: Cryo-EM structure of the human LYCHOS in complex with lipids in the expanded state 手法: EM (単粒子) / 解像度: 3.76 Å 61314 9jbh EMDB-61314, PDB-9jbh: Cryo-EM structure of the human LYCHOS PLD homodimer 手法: EM (単粒子) / 解像度: 2.73 Å 61315 9jbi EMDB-61315, PDB-9jbi: Cryo-EM structure of the human LYCHOS Y57A non-canonical dimer in the expanded state 手法: EM (単粒子) / 解像度: 4.49 Å 61316 9jbj EMDB-61316, PDB-9jbj: Cryo-EM structure of the human LYCHOS Y57A/R61A mutant in the expanded state 手法: EM (単粒子) / 解像度: 3.73 Å
化合物	ChemComp-Y01: CHOLESTEROL HEMISUCCINATE ChemComp-3PE: 1,2-Distearoyl-sn-glycerophosphoethanolamine / リン脂質YM ChemComp-CLR: CHOLESTEROL PDB-1l34: HIGH-RESOLUTION STRUCTURE OF THE TEMPERATURE-SENSITIVE MUTANT OF PHAGE LYSOZYME, ARG 96 (RIGHT ARROW) HIS ChemComp-PC1: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / リン脂質YM ChemComp-P5S: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine ChemComp-OLA: OLEIC ACID ChemComp-CDL: CARDIOLIPIN / リン脂質*YM
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / permease-like domain / GPCR-like domain / cholesterol / mTORC1