Diagram and model of predicted MPD structure and models of MIP1α–heparin complexes.

(A) An empirically determined structure for MPD is depicted based on the prevalence of particular-sized nitrous acid and heparinase-resistant fragments and frequencies of cleavage sites (Figure 6) and from information on fibroblast HS S-domain composition from sequencing studies.32 Pale blue spheres, GlcA-GlcNS; red spheres, IdoA(2S)-GlcNS; yellow spheres, IdoA(2S)-GlcNS(6S); green spheres, IdoA(± 2S)-GlcNAc; and deep blue spheres, GlcA-GlcNAc (see “Results” for abbreviations). This is roughly aligned with a model of MPD presented in an extended conformation. (B-D) Heparin ligand is in stick representation and MIP1α is shown rendered to display secondary structure; red α-helix, yellow β-strands, green random coil, and pale blue turns. Basic residues predicted to bind with heparin (Arg 17 on one loop, Arg 45 and Arg 47 on an adjacent loop) are shown in deep blue. (B) Dimeric MIP1α (pdb code 1B53) and (C) dimeric MIP-1α (model based on relative orientation of monomer subunits in PF4) docked with the energetically most favorably positioned heparin pentasaccharide ligand in each case. (D) Dimeric MIP-1α, as in panel C, docked with the energetically most favorable endecasaccharide.