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 language | English (US) |
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Pages (from-to) | 2663-2671 |
Number of pages | 9 |
Journal | Protein Science |
Volume | 8 |
Issue number | 12 |
DOIs | |
State | Published - 1999 |
Keywords
- Crystal structure
- Crystallization
- Fibrinogen
- Fusion protein
- Glutathione S-transferase
- Integrin
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry