5d9g

Crystal structure of TIPRL, TOR signaling pathway regulator-like, in complex with peptide

spinqualitylabelsall models 5d9g, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5d9g is a 4 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 2.15Å Ligands: CL, MSE, NI, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TIPRL_HUMAN May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Isoform 1 inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair. Publication Abstract from PubMed TOR signaling pathway regulator-like (TIPRL) is a regulatory protein which inhibits the catalytic subunits of Type 2A phosphatases. Several cellular contexts have been proposed for TIPRL, such as regulation of mTOR signaling, inhibition of apoptosis and biogenesis and recycling of PP2A, however, the underlying molecular mechanism is still poorly understood. We have solved the crystal structure of human TIPRL at 2.15 A resolution. The structure is a novel fold organized around a central core of antiparallel beta-sheet, showing an N-terminal alpha/beta region at one of its surfaces and a conserved cleft at the opposite surface. Inside this cleft, we found a peptide derived from TEV-mediated cleavage of the affinity tag. We show by mutagenesis, pulldown and hydrogen/deuterium exchange mass spectrometry that this peptide is a mimic for the conserved C-terminal tail of PP2A, an important region of the phosphatase which regulates holoenzyme assembly, and TIPRL preferentially binds the unmodified version of the PP2A-tail mimetic peptide DYFL compared to its tyrosine-phosphorylated version. A docking model of the TIPRL-PP2Ac complex suggests that TIPRL blocks the phosphatase's active site, providing a structural framework for the function of TIPRL in PP2A inhibition. Crystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus.,Scorsato V, Lima TB, Righetto GL, Zanchin NI, Brandao-Neto J, Sandy J, Pereira HD, Ferrari AJ, Gozzo FC, Smetana JH, Aparicio R Sci Rep. 2016 Aug 4;6:30813. doi: 10.1038/srep30813. PMID:27489114 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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