9kpb | pdb_00009kpb

Crystal structure of human CASTOR2 in apo form

spinqualitylabelsall models 9kpb, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9kpb 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: X-ray diffraction, Resolution 2.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth, responding to amino acid availability. While mTORC1 is modulated by amino acid sensors like CASTOR1, the mechanisms driving its dynamic response to fluctuating amino acid levels remain unclear. Here, we investigate the role of CASTOR2, an understudied CASTOR1 homolog, in regulating mTORC1 activity. We show that CASTOR1 and CASTOR2 bind to arginine similarly but differ in their sensitivity: CASTOR1 responds to low arginine levels, whereas CASTOR2 responds to high arginine concentrations. Both proteins interact with the GATOR2 component Mios, inhibiting its binding to GATOR1. Arginine binding to CASTOR1/2 induces conformational changes at the aspartate kinase, chorismate mutase, and TyrA (ACT) domain (ACT2-ACT4) interface, leading to its dissociation from Mios. Functionally, we demonstrate that CASTOR proteins are highly expressed in muscle tissue and, in C2C12 cells, they regulate mTORC1 and myogenesis in response to different arginine availability. These findings highlight how CASTOR proteins function as dual arginine sensors to fine-tune mTORC1 activity. CASTOR1 and CASTOR2 respond to different arginine levels to regulate mTORC1 activity.,Liu C, Zhang Y, Wang Y, Wu M, Li Y, Wei J, Shi J, Wang R, Su L, Yang T, Li J, Xiao J, Ding J, Zhang T Mol Cell. 2026 Jan 22;86(2):362-375.e4. doi: 10.1016/j.molcel.2025.12.016. Epub , 2026 Jan 7. PMID:41506264 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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