Plasmin cleaves FXIII-A₂* at multiple sites. (A) FXIII-A₂* cleavage sites were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI/TOF) mass spectrometry after purified FXIIIa (10 μM) was incubated with plasmin (2.7 μM) for 2 hours. Surface-exposed sites are represented with black bars, and the primary cleavage site with a red bar. The frequency of detection of cut sites is indicated beside the respective bars (n = 2). (B) A reported structure of FXIII-A₂*,¹⁴  showing the surface-exposed K468-Q469 cleavage site (red) and the catalytic cysteine (green). The distance between the cleavage site and the catalytic cysteine is 18 Å. (C) A reported structure of FXIII-A₂,¹³  showing K468-Q469 (red) and the activation peptide (blue).