Structure of the fibrinogen γ-chain integrin binding and factor XIIIa cross-linking sites obtained through carrier protein driven crystallization

Scott Ware, John P. Donahue, Jacek Hawiger, Wayne F. Anderson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The human fibrinogen γ-chain C-terminal segment functions as the platelet integrin binding site as well as the Factor XIIIa cross-linking substrate and thus plays an important role in blood clot formation and stabilization. The three-dimensional structure of this segment has been determined using carrier protein driven crystallization. The C-terminal segment, γ-(398-411), was attached to a linker sequence at the C-terminus of glutathione S-transferase and the structure of this fusion protein determined at 1.8 A resolution. Functional studies of the chimeric protein demonstrate that the fibrinogen sequence in the presence of the carrier protein retains its specific functions as ligand for platelet integrin {a11)β3 (gpIIb/IIIa) and as a cross-linking substrate for Factor XIIIa. The structure obtained for the fibrinogen γ-chain segment is not affected by crystal packing and can provide the missing links to the recently reported model of cross-linked fibrin.

Original languageEnglish (US)
Pages (from-to)2663-2671
Number of pages9
JournalProtein Science
Volume8
Issue number12
DOIs
StatePublished - 1999

Keywords

  • Crystal structure
  • Crystallization
  • Fibrinogen
  • Fusion protein
  • Glutathione S-transferase
  • Integrin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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