Figure 6.

Schematic thrombin cleavage of rhTPO. From the results of the time course analysis of the major thrombin–cleavage peptide fragments, rhTPO was cleaved at AR¹⁹¹–T¹⁹² first, and TPO[1–191] was generated. Subsequently, the generated TPO[1–191] was also cleaved by prolonged thrombin digestion at GR¹¹⁷–T¹¹⁸ in the N-terminal domain. The biological activity of the resultant proteins are consequently modulated by the thrombin cleavage. Thrombin may directly cleave rhTPO at GR¹¹⁷–T¹¹⁸ without the cleavage at AR¹⁹¹–T¹⁹², as indicated by the dotted arrow; however, structurally this site is more resistant against thrombin cleavage than the AR¹⁹¹–T¹⁹² site. Disulfide bonds (C⁷–C¹⁵¹ and C²⁹–C⁸⁵) are indicated by S–S loops.