8Y56

Cryo-EM reveals cholesterol binding in the lysosomal GPCR-like protein LYCHOS

Summary for 8Y56

• Entry DOI: 10.2210/pdb8y56/pdb
• EMDB information: 38930
• Descriptor: Lysosomal cholesterol signaling protein, SODIUM ION, CHOLESTEROL, ... (5 entities in total)
• Functional Keywords: cholesterol, membrane protein, lysosome
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 96552.65

Authors

Zhao, J.,Shen, Q.Y.,Zhang, Y.,Shao, Z.H. (deposition date: 2024-01-31, release date: 2025-01-29, Last modification date: 2025-06-04)

Primary citation

Zhao, J.,Shen, Q.,Yong, X.,Li, X.,Tian, X.,Sun, S.,Xu, Z.,Zhang, X.,Zhang, L.,Yang, H.,Shao, Z.,Xu, H.,Jiang, Y.,Zhang, Y.,Yan, W.
Cryo-EM reveals cholesterol binding in the lysosomal GPCR-like protein LYCHOS.
Nat.Struct.Mol.Biol., 32:896-904, 2025

PubMed Abstract: Cholesterol plays a pivotal role in modulating the activity of mechanistic target of rapamycin complex 1 (mTOR1), thereby regulating cell growth and metabolic homeostasis. LYCHOS, a lysosome-localized G-protein-coupled receptor-like protein, emerges as a cholesterol sensor and is capable of transducing the cholesterol signal to affect the mTORC1 function. However, the precise mechanism by which LYCHOS recognizes cholesterol remains unknown. Here, using cryo-electron microscopy, we determined the three-dimensional structural architecture of LYCHOS in complex with cholesterol molecules, revealing a unique arrangement of two sequential structural domains. Through a comprehensive analysis of this structure, we elucidated the specific structural features of these two domains and their collaborative role in the process of cholesterol recognition by LYCHOS.

PubMed: 39824976
DOI: 10.1038/s41594-024-01470-9

Experimental method

ELECTRON MICROSCOPY (2.83 Å)