8y56

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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.
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.
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Cryo-EM reveals cholesterol binding in the lysosomal GPCR-like protein LYCHOS.,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 Nat Struct Mol Biol. 2025 Jan 17. doi: 10.1038/s41594-024-01470-9. PMID:39824976<ref>PMID:39824976</ref>
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, PMID:39824976<ref>PMID:39824976</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 09:14, 4 June 2025

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

PDB ID 8y56

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