Unique degradation of human fibrinogen by proteases from western diamondback rattlesnake (Crotalus atrox) venom.

Thrombin-coagulability of both human fibrinogen and plasma was rapidly lost upon incubation with western diamondback rattlesnake (Crotalus atrox) venom. The dose- and time-dependent effect was due to direct proteolytic degradation of fibrinogen (Mr 340,000) by venom enzymes. Using purified fibrinogen as the substrate it was demonstrated that the venom degraded the A alpha chain first and then the B beta chain. The degradation pattern of fibrinogen in plasma was different to that of purified fibrinogen, since only the B beta chain was cleaved. A fibrinogen derivative isolated from venom-treated plasma had impaired thrombin-coagulability, Mr 325,000 +/- 10,000, its A alpha and gamma chains appeared intact and only the B beta chain was degraded to a species of Mr 52,000 +/- 1,500. The venom contained three proteolytic enzyme fractions as revealed by gel filtration chromatography. All abolished coagulability of purified fibrinogen, however, only one enzyme fraction rendered plasma incoagulable. The proteolytic enzyme with anticoagulant activity against plasma degraded only the B beta chain of purified fibrinogen, generating a derivative of Mr 325,000, which was identical to that obtained upon incubation of the crude venom with plasma. The polypeptide chain structure of the derivative indicates that the intact B beta chain of fibrinogen plays an important role in the formation of fibrin clots.