6ssh

Structure of the TSC2 GAP domain

spinqualitylabelsall models 6ssh, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ssh is a 1 chain structure with sequence from Chaetomium thermophilum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G0SFF5_CHATD Publication Abstract from PubMed The TSC complex is the cognate GTPase-activating protein (GAP) for the small GTPase Rheb and a crucial regulator of the mechanistic target of rapamycin complex 1 (mTORC1). Mutations in the TSC1 and TSC2 subunits of the complex cause tuberous sclerosis complex (TSC). We present the crystal structure of the catalytic asparagine-thumb GAP domain of TSC2. A model of the TSC2-Rheb complex and molecular dynamics simulations suggest that TSC2 Asn1643 and Rheb Tyr35 are key active site residues, while Rheb Arg15 and Asp65, previously proposed as catalytic residues, contribute to the TSC2-Rheb interface and indirectly aid catalysis. The TSC2 GAP domain is further stabilized by interactions with other TSC2 domains. We characterize TSC2 variants that partially affect TSC2 functionality and are associated with atypical symptoms in patients, suggesting that mutations in TSC1 and TSC2 might predispose to neurological and vascular disorders without fulfilling the clinical criteria for TSC. Structure of the TSC2 GAP Domain: Mechanistic Insight into Catalysis and Pathogenic Mutations.,Hansmann P, Bruckner A, Kiontke S, Berkenfeld B, Seebohm G, Brouillard P, Vikkula M, Jansen FE, Nellist M, Oeckinghaus A, Kummel D Structure. 2020 Jun 4. pii: S0969-2126(20)30177-5. doi:, 10.1016/j.str.2020.05.008. PMID:32502382 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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