Jie Zhao, Qingya Shen, Xihao Yong, Xin Li, Xiaowen Tian, Suyue Sun, Zheng Xu, Xiaoyu Zhang, Lu Zhang, Hao Yang, Zhenhua Shao, Haoxing Xu, Yiyang Jiang, Yan Zhang, Wei Yan
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引用次数: 0
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.
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