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Membrane cofactor protein: importance of N- and O-glycosylation for complement regulatory function
M K Liszewski1, M K Leung, J P Atkinson
1Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 6, 1998
Summary
Carbohydrates on membrane cofactor protein (MCP; CD46) are crucial for its complement regulatory function. N-glycans on CCP-2 and CCP-4 are necessary for protecting host cells from complement-mediated lysis.
Area of Science:
- Immunology
- Glycobiology
- Molecular Biology
Background:
- Membrane cofactor protein (MCP; CD46) is a glycoprotein that regulates complement activation on host cells.
- MCP also functions as a receptor for measles virus and adherence factor for bacteria.
- MCP contains complement control protein (CCP) repeats and an alternatively spliced STP domain, with varying glycosylation patterns.
Purpose of the Study:
- To investigate the role of carbohydrates (N-glycans and O-glycans in the STP domain) in MCP's complement regulatory function.
- To determine which specific carbohydrate structures are essential for MCP's cytoprotective activity.
Main Methods:
- Constructed and expressed MCP variants with specific carbohydrate deletions.
- Characterized the complement regulatory function of these variants.
- Assessed the cleavage of C4b to C4c and C4d by MCP and factor I.
Main Results:
- N-glycans on CCP-2 and CCP-4 were essential for MCP-mediated protection against cytolysis.
- The STP domain influenced but was not essential for cytoprotection.
- N-glycans on CCP-1 were not required for complement regulation.
- Cleavage of C4b correlated with cytoprotection.
Conclusions:
- Carbohydrates, particularly N-glycans on CCP-2 and CCP-4, play a critical role in MCP's complement regulatory function.
- These findings enhance the understanding of MCP's structure-function relationship and the importance of glycosylation in its activity.