{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang J"],"funding":["Kirsten og Freddy Johansens Fond","Købmand I Odense Johan og Hanne Weimann Født Seedorffs Legat","Novo Nordisk","Alfred Benzon Foundation","Lundbeck Foundation"],"pagination":["e60908"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7511233"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9"],"pubmed_abstract":["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."],"journal":["eLife"],"pubmed_title":["Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement."],"pmcid":["PMC7511233"],"funding_grant_id":["R155-2015-2666","Research fund"],"pubmed_authors":["Song L","Andersen GR","Ma YJ","Zhang J","Garred P","Li A","Pedersen DV","Lambris JD","Mollnes TE"],"additional_accession":[]},"is_claimable":false,"name":"Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement.","description":"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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Sep","modification":"2024-11-10T00:47:56.435Z","creation":"2020-09-30T07:06:19Z"},"accession":"S-EPMC7511233","cross_references":{"pubmed":["32909942"],"doi":["10.7554/eLife.60908"]}}