8dhb

Active FLCN GAP complexActive FLCN GAP complex

Structural highlights 8dhb is a 10 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 3.53Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth and catabolism in response to nutrients through phosphorylation of key substrates. The tumor suppressor folliculin (FLCN) is a RagC/D guanosine triphosphatase (GTPase)-activating protein (GAP) that regulates mTORC1 phosphorylation of MiT-TFE transcription factors, controlling lysosome biogenesis and autophagy. We determined the cryo-electron microscopy structure of the active FLCN complex (AFC) containing FLCN, FNIP2, the N-terminal tail of SLC38A9, the RagA(GDP):RagC(GDP.BeFx-) GTPase dimer, and the Ragulator scaffold. Relative to the inactive lysosomal FLCN complex structure, FLCN reorients by 90 degrees , breaks contact with RagA, and makes previously unseen contacts with RagC that position its Arg(164) finger for catalysis. Disruption of the AFC-specific interfaces of FLCN and FNIP2 with RagC eliminated GAP activity and led to nuclear retention of TFE3, with no effect on mTORC1 substrates S6K or 4E-BP1. The structure provides a basis for regulation of an mTORC1 substrate-specific pathway and a roadmap to discover MiT-TFE family selective mTORC1 antagonists. Structural basis for FLCN RagC GAP activation in MiT-TFE substrate-selective mTORC1 regulation.,Jansen RM, Peruzzo R, Fromm SA, Yokom AL, Zoncu R, Hurley JH Sci Adv. 2022 Sep 16;8(37):eadd2926. doi: 10.1126/sciadv.add2926. Epub 2022 Sep , 14. PMID:36103527 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also GTP-binding protein 3D structures Glutathione S-transferase 3D structures Ragulator complex 3D structures

spinqualitylabelsall models 8dhb, resolution 3.53Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image