Figure 3

Structural model of DNAJB6 dimer. (A) The structural model of DNAJB6 monomer (selected as best fit, Fig. 1) in ribbon presentation (grey) with lysine residues as spheres: K189 (dark red), K232 (dark blue), K202 (light blue), K225 (light red). The inter-subunit crosslinks K189-K189 and K232-K232 (Table 2) were used as restraints in docking. (B) The DNAJB6 dimer model as cartoon, with the two subunits in yellow and blue, respectively. The lysine residues K189 and K232 (spheres, color coded according to each subunit) are shown with the inter-subunit crosslinks indicated with dashed lines, with distances K189-K189 = 23.5 Å and K232-K232 = 20.6 Å. The following residues are shown as sticks: N199, G200 (black); the S/T-residues S-STST aa 190, 192–195 (dark pink); other ST-residues in region aa 155–195 (light pink). The two symmetrically positioned β-hairpins (=β-strand 1 and 2 and the residues N199 and G200 in between) contain the functionally essential S/T residues. (C) The DNAJB6 dimer model in surface presentation color-coded as in (B), showing a central cleft between the domains which could serve as a peptide-binding cleft, surrounded by S/T-residues, S-STST aa 190, 192–195 (dark pink); other ST-residues in region aa 155–195 (light pink). (D) The DNAJB6 dimer model in spacefill presentation (grey) and one copy of Aβ42-peptide (red, with residues K16 and K28 as sticks). The image is obtained after HADDOCK docking of the Aβ42 (PDB ID 2NAO, shown as inset with the two K16 and K28 highlighted in red) to the DNAJB6 dimer model, using as restraints the crosslinked residues (K16 and K28 in Aβ42, K189, K232, K202 and K225 in one of the DNAJB6 dimer subunits).