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Identification of a Novel Inhibitory Allosteric Site in p38α

Fig 1

Scheme of the interaction between p38α and MK2 as proposed by teer Haar et al. [11].

(i) In the nucleus of the cell p38α and MK2 can form a heterodimer that prevents both proteins to phosphorylate their respective substrates. Crystal structures with PDB codes 2OZA [10] and 2ONL [11] may constitute representative structures of this heterodimer present in the nucleus. (ii) Alternatively p38α can interact with MKK3 or MKK6 (iii) to be phosphorylated by the action of them. (iv) Once p38α is phosphorylated on residues T180 and Y182, it can form an alternative heterodimer with MK2, (vi) which will induce phosphorylation of MK2 residues T25, T222, T272 and T334 by p38α. Phosphorylation of MK2 in residue T334 (grey phosphate) induces a conformational change that makes its nuclear export signal (NES) accessible, permitting the p38-MK2 heterodimer to be translocated to the cytoplasm, where they can phosphorylate diverse substrates. V) Alternatively, the dimer can dissociate in the nucleus and both proteins will phosphorylate diverse substrates until a phosphatase dephosphorylates them.

Fig 1

doi: https://doi.org/10.1371/journal.pone.0167379.g001