Identification of substrates of MBL Associated Serine Protease-1 (MASP-1) from human plasma using N-terminomics strategy

Abstract

Mbl associated serine protease-1 (masp-1) is an abundant enzyme of the lectin complement pathway. Masp-1 cleaves numerous substrates like masp-2, masp-3, c2, c3i, fibrinogen, fxiii and prothrombin. It has thrombin-like specificity and can cleave thrombin substrates. Owing to its high concentration and relaxed substrate specificity, masp-1 has substrates outside the complement system and can influence other proteolytic cascades and physiological processes. The unidentified substrates may assist us to ascertain the role(s) of masp-1. In this study, we used a high-throughput n-terminomics method to identify substrates of masp-1 from human plasma. We have identified 35 putative substrates of masp-1. Among the identified proteins, alpha 2-antiplasmin, alpha-1-acid glycoprotein, antithrombin iii, and siglec-6 were demonstrated to be cleaved by masp-1. We have discussed the physiological relevance of cleavage of these substrates by masp-1. The expression of siglec-6 and masp-1 has been reported in the b cells. Alpha-1-acid glycoprotein cleavage by masp-1 may occur in the acute phase as it is known to be an inhibitor of platelet aggregation, whereas masp-1 triggers platelet aggregation. The cleavage alpha2 antiplasmin by masp-1 implies that masp-1 may be promoting plasmin-mediated fibrinolysis. Our study supports that masp-1 may be implicated in thrombosis as well as thrombolysis. © 2022 elsevier ltd