MAp44, a human protein associated with pattern recognition molecules of the complement system and regulating the
Søren E Degn1, Annette G Hansen, Rudi Steffensen
1Departments of Medical Microbiology and Immunology, University of Aarhus, Arhus, Denmark.
Journal of Immunology (Baltimore, Md. : 1950)
|November 18, 2009
Summary
A novel protein, MAp44, binds to mannan-binding lectin (MBL) and ficolins, inhibiting complement activation. This discovery reveals a new regulatory mechanism for the innate immune system.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Innate immunity relies on complement activation initiated by pattern recognition molecules like mannan-binding lectin (MBL) and ficolins.
- Understanding the regulation of complement activation is crucial for controlling immune responses.
Purpose of the Study:
- To identify and characterize a novel protein involved in the regulation of innate immunity.
- To elucidate the mechanism by which this new protein interacts with complement system components.
Main Methods:
- Surface plasmon resonance was used to determine binding affinity.
- Gene expression profiling was performed using mRNA analysis in human tissues.
- Biochemical assays were conducted to assess complement activation inhibition.
Main Results:
- A novel, conserved protein, MAp44, was identified in human serum, forming Ca(2+)-dependent complexes with MBL and ficolins.
- MAp44 exhibits high-affinity binding to MBL (K(D) = 0.6 nM).
- MAp44 inhibits complement activation by competing with MASP-2 for binding to MBL and ficolins.
Conclusions:
- MAp44 represents a novel regulator of the lectin pathway of complement activation.
- This finding introduces a new mechanism controlling innate immune responses.
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