Abstract
Fibrinogen mediates the processes of platelet aggregation and clot retraction. Previous studies have demonstrated that fibrinogen binding to the platelet receptor alphaIIbbeta3 requires the C-terminal residues of the fibrinogen gamma chain. We made a recombinant human fibrinogen that lacks the gamma chain C-terminal four residues (AGDV). As expected this fibrinogen did not support platelet aggregation. Unexpectedly, this variant did support clot retraction that was indistinguishable from retraction with normal recombinant or plasma fibrinogen. These results suggest that the site on fibrinogen that is required for platelet aggregation differs from the site on fibrin that is required for clot retraction.
Highlights
Fibrinogen mediates the processes of platelet aggregation and clot retraction
Previous work employing electron microscopy [2], synthetic peptides [3], and recombinant proteins [4, 5] has implicated the D domain, in particular residues ␥408 – 411 (AGDV), as the site on fibrinogen that interacts with platelets
We report that an intact recombinant fibrinogen lacking only residues ␥408 – 411 does not support aggregation, consistent with previous work [4, 5], but unexpectedly supports clot retraction to the same extent as normal recombinant and plasma fibrinogen
Summary
(Received for publication, December 13, 1995, and in revised form, February 16, 1996). Previous work employing electron microscopy [2], synthetic peptides [3], and recombinant proteins [4, 5] has implicated the D domain, in particular residues ␥408 – 411 (AGDV), as the site on fibrinogen that interacts with platelets This interaction involves the platelet integrin ␣IIb3, a heterodimeric transmembrane receptor. We report that an intact recombinant fibrinogen lacking only residues ␥408 – 411 does not support aggregation, consistent with previous work [4, 5], but unexpectedly supports clot retraction to the same extent as normal recombinant and plasma fibrinogen. These findings suggest that other domains in fibrinogen participate in clot retraction
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