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

Amit Sharma, Janet A Askari, Martin J Humphries, E. Yvonne Jones, David I. Stuart

Research output: Contribution to journalArticlepeer-review


The crystal structure of human fibronectin (FN) type III repeats 12-14 reveals the primary heparin-binding site, a clump of positively charged residues in FN13, and a putative minor site ~ 60 Å away in FN14. The IDAPS motif implicated in integrin α4β1 binding is at the FN13-14 junction, rendering the critical Asp184 inaccessible to integrin. Asp184 clamps the BC loop of FN14, whose sequence (PRARI) is reminiscent of the synergy sequence (PHSRN) of FN9. Mutagenesis studies prompted by this observation reveal that both arginines of the PRARI sequence are important for α4β1 binding to FN12-14. The PRARI motif may represent a new class of integrin-binding sites. The spatial organization of the binding sites suggests that heparin and integrin may bind in concert.
Original languageEnglish
Pages (from-to)1468-1479
Number of pages11
JournalEMBO Journal
Issue number6
Publication statusPublished - 15 Mar 1999


  • Fibronectin
  • Heparin binding
  • Integrin binding
  • Protein structure
  • Type III


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