Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural insights into cholesterol sensing by the LYCHOS-mTORC1 pathway.
Journal, issue, pages	Nat Commun, Vol. 16, Issue 1, Page 6792, Year 2025
Publish date	Jul 23, 2025
Authors	Shang Yu / Jin-Hui Ding / Jia-le Wang / Weize Wang / Peng Zuo / Ao Yang / Zonglin Dai / Yuxin Yin / Jin-Peng Sun / Ling Liang /
PubMed Abstract	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.
External links	Nat Commun / PubMed:40702016 / PubMed Central
Methods	EM (single particle)
Resolution	2.73 - 4.49 Å
Structure data	61311 9jbe EMDB-61311, PDB-9jbe: Cryo-EM structure of the human LYCHOS in complex with cholesterol and cholesteryl hemisuccinate in the contracted state Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 3.21 Å 61313 9jbg EMDB-61313, PDB-9jbg: Cryo-EM structure of the human LYCHOS in complex with lipids in the expanded state Method: EM (single particle) / Resolution: 3.76 Å 61314 9jbh EMDB-61314, PDB-9jbh: Cryo-EM structure of the human LYCHOS PLD homodimer Method: EM (single particle) / Resolution: 2.73 Å 61315 9jbi EMDB-61315, PDB-9jbi: Cryo-EM structure of the human LYCHOS Y57A non-canonical dimer in the expanded state Method: EM (single particle) / Resolution: 4.49 Å 61316 9jbj EMDB-61316, PDB-9jbj: Cryo-EM structure of the human LYCHOS Y57A/R61A mutant in the expanded state Method: EM (single particle) / Resolution: 3.73 Å
Chemicals	ChemComp-Y01: CHOLESTEROL HEMISUCCINATE ChemComp-3PE: 1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipidYM 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 / phospholipidYM ChemComp-P5S: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine ChemComp-OLA: OLEIC ACID ChemComp-CDL: CARDIOLIPIN / phospholipid*YM
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / permease-like domain / GPCR-like domain / cholesterol / mTORC1