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C1s proenzyme is a single chain 86,000 dalton protein that is the native form of C1s enzyme.C1s is a subunit of the C1 complex which is the first complement component in the cascade referred to as the classical pathway of complement.C1s proenzyme is an inactive zymogen until C1 is activated.C1 complex binds to and is activated by antigen-antibody complexes (immune complexes) yielding C1r enzyme.C1r enzyme in the C1 complex activates C1s proenzyme generating C1s enzyme.C1 complex is a non-covalent calcium-dependent complex of one C1q, two C1r and two C1s molecules.C1q binds through two or more of its six arms to the Fc domains of IgG or IgM.The binding of multiple arms to immune complexes causes the two C1r proteins in the complex (protease zymogens) to activate producing two proteases that cleave and activate the two C1s proenzymes in the complex (Morikis, D. and Lambris, J.D. (2005)).This activation of C1s proenzyme is caused by cleavage into the two chain C1s enzyme with 58,000 and 28,000 dalton fragments.
Activated C1s enzyme cleaves complement component C4 releasing C4a and initiating covalent attachment of C4b to the activating surface.Activated C1s also cleaves C2 and the larger fragment of C2 binds to the surface-attached C4b forming C4b,C2a, the C3/C5 convertase of the classical pathway.
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