Fig. 5: Structure of the pp-p38:ATF2(SPFENEF) complex.
From: Co-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38
a Crystal structure of the pp-p38:ATF2(83–102)_S90N complex. Residues between 88 and 101 are visible in the crystal structure as shown in the simulated annealing Fo-Fc omit map contoured at 2ϭ. b The helical ATF2 peptide is wedged in-between the N-terminal parts of the αG and α2L14 helices. The F-motif recruitment site (FRS) pocket (accommodating two phenylalanines, F92 and F96) is lined by activation loop residues (e.g., pY182) and W197. c Nonphosphorylated (np-p38) and phosphorylated p38 (pp-p38) crystal structures show a major difference in the orientation of the αEF/αF loop with W197. In the nonphosphorylated protein the FRS pocket is blocked by W197, while in the phosphorylated protein it forms the upper rim of this pocket together with the phosphorylated activation loop (AL). d Structural model of the pp-p38:WT-ATF2(TAD)complex. The model was generated using ambiguous restraints derived from NMR titration data on pp-38 and SPFENEF motif peptide. Zinc-finger + D-motif (yellow + cyan) and substrate peptide (T69 as the target site, red) were docked using unambiguous distance restraints (DRS: D-motif recruitment site). e S90 caps the ATF2 helix and is located at a critical position: phosphorylation at this site sterically blocks the binding interface and affects the conformation of the unbound peptide (Supplementary Fig. 6b). In addition, the two glutamate side-chains (E93 and E95) cap α2L14 and αG, and these hydrogen bonds are shown with dashed lines. f Structural basis of increased, non-regulatable binding for the invertebrate NPFENEF motif. An asparagine (N) at 90 is structurally more optimal compared to serine.
