Crystal structure of a heparin- and integrin-binding segment of human fibronectin

The crystal structure of human fibronectin (FN) type III repeats 12-14 reve als the primary heparin-binding site, a clump of positively charged residue s in FN13, and a putative minor site similar to 60 Angstrom away in FN14. T he IDAPS motif implicated in integrin alpha(4)beta(1) binding is at the FN1 3-14 junction, rendering the critical Asp184 inaccessible to integrin. Asp1 84 clamps the BC loop of FN14, whose sequence (PRARI) is reminiscent of the synergy sequence (PHSRN) of FN9. Mutagenesis studies prompted by this obse rvation reveal that both arginines of the PRARI sequence are important for alpha(4)beta(1) binding to FN12-14. The PRARI motif may represent a new cla ss of integrin-binding sites, The spatial organization of the binding sites suggests that heparin and integrin may bind in concert.