7nry
From Proteopedia
Re-refinement of MAPKAP kinase-2/inhibitor complex 3fyj
Structural highlights
FunctionMAPK2_HUMAN Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Publication Abstract from PubMedWhen building atomic models into weak and/or low-resolution density, a common strategy is to restrain their conformation to that of a higher resolution model of the same or similar sequence. When doing so, it is important to avoid over-restraining to the reference model in the face of disagreement with the experimental data. The most common strategy for this is the use of `top-out' potentials. These act like simple harmonic restraints within a defined range, but gradually weaken when the deviation between the model and reference grows beyond that range. In each current implementation the rate at which the potential flattens at large deviations follows a fixed form, although the form chosen varies among implementations. A restraint potential with a tuneable rate of flattening would provide greater flexibility to encode the confidence in any given restraint. Here, two new such potentials are described: a Cartesian distance restraint derived from a recent generalization of common loss functions and a periodic torsion restraint based on a renormalization of the von Mises distribution. Further, their implementation as user-adjustable/switchable restraints in ISOLDE is described and their use in some real-world examples is demonstrated. Adaptive Cartesian and torsional restraints for interactive model rebuilding.,Croll TI, Read RJ Acta Crystallogr D Struct Biol. 2021 Apr 1;77(Pt 4):438-446. doi:, 10.1107/S2059798321001145. Epub 2021 Mar 30. PMID:33825704[17] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations 0 reviews cite this structure No citations found References
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