8y56

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

spinqualitylabelsall models 8y56, resolution 2.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8y56 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.83Å Ligands: CLR, DKB, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LYCHS_HUMAN Cholesterol-binding protein that acts as a regulator of mTORC1 signaling pathway (PubMed:36007018). Acts as a sensor of cholesterol to signal cholesterol sufficiency to mTORC1: in presence of cholesterol, binds cholesterol, leading to disrupt interaction between the GATOR1 and KICSTOR complexes and promote mTORC1 signaling (PubMed:36007018). Upon cholesterol starvation, GPR155/LYCHOS is unable to perturb the association between GATOR1 and KICSTOR, leading to mTORC1 signaling inhibition (PubMed:36007018). Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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