Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement
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- elife-60908-v3
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Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern-recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, whether this observation is C3 dependent is unknown. By application of the C3-inhibitor Cp40, we found that properdin in normal human serum bound to Aspergillus fumigatus solely in a C3b-dependent manner. Cp40 also prevented properdin binding when properdin-depleted serum reconstituted with purified properdin was applied, in analogy with the findings achieved by C3-depleted serum. However, when opsonized with sCL-12, properdin bound in a C3-independent manner exclusively via its tetrameric structure and directed in situ C3bBb assembly. In conclusion, a prerequisite for properdin binding and in situ C3bBb assembly was the initial docking of sCL-12. This implies a new important function of properdin in host defense bridging pattern recognition and specific AP activation.
Original language | English |
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Article number | e60908 |
Journal | eLife |
Volume | 9 |
Number of pages | 19 |
ISSN | 2050-084X |
DOIs | |
Publication status | Published - 2020 |
Bibliographical note
© 2020, Zhang et al.
- Aspergillus fumigatus/immunology, Collectins/blood, Complement C3/metabolism, Complement Pathway, Alternative/immunology, HEK293 Cells, Humans, Properdin/analysis, Protein Binding/immunology
Research areas
ID: 269535633