Figure 7.
Working model of HAI-1. A, models of membrane-bound HAI-1 and its variants. Left, the models of sHAI-1 of the 58- and 40/39-kDa forms. Right, the membrane-bound model of HAI-1. B, membrane-bound form HAI-1 in complex with activated matriptase in two chain form. Matriptase is a cell surface glycoprotein type II transmembrane serine protease, consisting of an N-terminal cytoplasmic domain, a signal-anchor transmembrane domain, a non-catalytic stem domain (containing a SEA domain, two CUB domains, and four LDLRA domains), and a C-terminal SPD. Matriptase is synthesized as a zymogen and is completely activated by cleavage at Gly149–Ser150 and Arg614–Val615. HAI-1 inhibited the activated matriptase with its Kunitz domain 1 forming a tight non-covalent complex with SPD. Additional interactions are found between the CUB2 domain and Kunitz domain 2. SEA, sea urchin sperm protein, enteropeptidase, agrin; CUB, complement C1r/C1s-urchi embryonic growth factor, bone morphogenetic protein 1.