Fig. 1
PAM directly binds to HMGB1 and CXCL12 and disrupts their heterocomplex. A Histogram showing residue-specific CSPs of 15N-HMGB1 (~ 0.1 mM) upon addition of equimolar ratio of PAM (helices are schematically represented on top). Missing residues are prolines or are absent because of exchange with the solvent. BoxA and BoxB residues with CSP > Avg + SD are represented in magenta and light blue, respectively. HADDOCK models of interaction of PAM (licorice representation) with BoxA (middle) and BoxB (right) (gray surface and colored residues with CSP > Avg + SD). HMGB1 residues (sticks) involved in hydrophobic and electrostatic interactions with PAM are labeled. B Histogram showing the CSPs of 15N-CXCL12 amides (~ 0.1 mM) upon addition of equimolar ratio of PAM. Missing residues are prolines. Elements of secondary structure are represented on top. Middle: HADDOCK model of interaction of PAM (CPK representation) with CXCL12 (gray surface). CXCL12 residues with CSP > Avg + SD located around the sY21 binding site are in orange. Right: Zoom in the binding site, CXCL12 residues (sticks) involved in hydrophobic and electrostatic interactions with PAM (sticks) are explicitly labeled. C Selected region of 1H-15N HSQC HMGB1 (0.1 mM) spectrum without (black, left), with 0.2 mM CXCL12 (red, middle) and upon addition of 0.05 mM PAM (blue, right)