5w0x | pdb_00005w0x

Crystal structure of mouse TOR signaling pathway regulator-like (TIPRL) delta 94-103

spinqualitylabelsall models 5w0x, resolution 2.72Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5w0x is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.717Å Ligands: MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TIPRL_MOUSE May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AFX phosphorylated on Ser-140 (gamma-H2AFX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair (By similarity).[UniProtKB:O75663] Publication Abstract from PubMed Dynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site. TIPRL also makes unusual wobble contacts with the scaffold subunit, allowing TIPRL, but not the overlapping regulatory subunits, to tolerate disease-associated PP2A mutations, resulting in reduced holoenzyme assembly and enhanced inactivation of mutant PP2A. Strikingly, TIPRL and the latency chaperone, alpha4, coordinate to disassemble active holoenzymes into latent PP2A, strictly controlled by methylation. Our study reveals a mechanism for methylation-responsive inactivation and holoenzyme disassembly, illustrating the complexity of regulation/signaling, dynamic complex disassembly, and disease mutations in cancer and intellectual disability. Methylation-regulated decommissioning of multimeric PP2A complexes.,Wu CG, Zheng A, Jiang L, Rowse M, Stanevich V, Chen H, Li Y, Satyshur KA, Johnson B, Gu TJ, Liu Z, Xing Y Nat Commun. 2017 Dec 22;8(1):2272. doi: 10.1038/s41467-017-02405-3. PMID:29273778 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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