Abstract
The complement system is a major effector arm of the immune defense contributing to the destruction of invading pathogens. There are three possible routes of complement cascade activation the classical, the alternative and the lectin pathways. The activation of the classical and lectin pathways is initiated by supramolecular complexes, which resemble each other. Each complex has a recognition subunit (C1q in the classical and mannose-binding lectin (MBL) in the lectin pathway), which associates with serine protease zymogens (C1q with C1r and C1s, and MBL with MBL-associated serine proteases MASP-1, MASP-2) to form the C1 and MBL-MASPs complexes, respectively. As the recognition subunits bind to activator structures, subsequent activation of the serine protease zymogens occurs. The precise structure of the complexes and the exact mechanism of their activation have not been solved, yet. In this review we summarize the recent advances about the structure and function of the individual subcomponents of both complexes achieved by genetic engineering, molecular modeling, physico-chemical and functional studies. Special emphasis will be laid on the serine proteases the role of the individual domains in the assembly of the C1s-C1r-C1r-C1s tetramer and in the control of the protease activity will be discussed. We will then focus on recent functional models of the supramolecular complexes. The question of how a non-enzymatic signal (the binding of C1q or MBL to activators) can be converted into enzymatic events (activation of serine protease zymogens) will be addressed. The similarities and differences between C1 and MBL-MASPs will also be discussed.
Keywords: Complexes C1, MBL MASPs, serine, protease zymogens, MBL associated serine proteases, serine protease zymogens
Current Protein & Peptide Science
Title: Structure and Function of Complement Activating Enzyme Complexes C1 and MBL-MASPs
Volume: 2 Issue: 1
Author(s): P. GAL and G. Ambrus
Affiliation:
Keywords: Complexes C1, MBL MASPs, serine, protease zymogens, MBL associated serine proteases, serine protease zymogens
Abstract: The complement system is a major effector arm of the immune defense contributing to the destruction of invading pathogens. There are three possible routes of complement cascade activation the classical, the alternative and the lectin pathways. The activation of the classical and lectin pathways is initiated by supramolecular complexes, which resemble each other. Each complex has a recognition subunit (C1q in the classical and mannose-binding lectin (MBL) in the lectin pathway), which associates with serine protease zymogens (C1q with C1r and C1s, and MBL with MBL-associated serine proteases MASP-1, MASP-2) to form the C1 and MBL-MASPs complexes, respectively. As the recognition subunits bind to activator structures, subsequent activation of the serine protease zymogens occurs. The precise structure of the complexes and the exact mechanism of their activation have not been solved, yet. In this review we summarize the recent advances about the structure and function of the individual subcomponents of both complexes achieved by genetic engineering, molecular modeling, physico-chemical and functional studies. Special emphasis will be laid on the serine proteases the role of the individual domains in the assembly of the C1s-C1r-C1r-C1s tetramer and in the control of the protease activity will be discussed. We will then focus on recent functional models of the supramolecular complexes. The question of how a non-enzymatic signal (the binding of C1q or MBL to activators) can be converted into enzymatic events (activation of serine protease zymogens) will be addressed. The similarities and differences between C1 and MBL-MASPs will also be discussed.
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Cite this article as:
GAL P. and Ambrus G., Structure and Function of Complement Activating Enzyme Complexes C1 and MBL-MASPs, Current Protein & Peptide Science 2001; 2 (1) . https://dx.doi.org/10.2174/1389203013381242
DOI https://dx.doi.org/10.2174/1389203013381242 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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