4lac

Crystal Structure of Protein Phosphatase 2A (PP2A) and PP2A phosphatase activator (PTPA) complex with ATPgammaS

spinqualitylabelsall models 4lac, resolution 2.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4lac is a 3 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 2.82Å Ligands: AGS, MES, MN, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PTPA_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine-protein phosphatase 2A (PP2A) modulating its activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg(2+) (By similarity). Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A. Publication Abstract from PubMed Proper activation of protein phosphatase 2A (PP2A) catalytic subunit is central for the complex PP2A regulation and is crucial for broad aspects of cellular function. The crystal structure of PP2A bound to PP2A phosphatase activator (PTPA) and ATPgammaS reveals that PTPA makes broad contacts with the structural elements surrounding the PP2A active site and the adenine moiety of ATP. PTPA-binding stabilizes the protein fold of apo-PP2A required for activation, and orients ATP phosphoryl groups to bind directly to the PP2A active site. This allows ATP to modulate the metal-binding preferences of the PP2A active site and utilize the PP2A active site for ATP hydrolysis. In vitro, ATP selectively and drastically enhances binding of endogenous catalytic metal ions, which requires ATP hydrolysis and is crucial for acquisition of pSer/Thr-specific phosphatase activity. Furthermore, both PP2A- and ATP-binding are required for PTPA function in cell proliferation and survival. Our results suggest novel mechanisms of PTPA in PP2A activation with structural economy and a unique ATP-binding pocket that could potentially serve as a specific therapeutic target.Cell Research advance online publication 8 October 2013; doi:10.1038/cr.2013.138. Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone.,Guo F, Stanevich V, Wlodarchak N, Sengupta R, Jiang L, Satyshur KA, Xing Y Cell Res. 2013 Oct 8. doi: 10.1038/cr.2013.138. PMID:24100351 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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