title: Prohibitin binds to C3 and enhances complement activation.
abstract: Prohibitin (PHB1) is a multifunction protein that is released in lipid droplets from adipocytes and possibly other cells and is detectable in the circulation. We used crosslinking, immunoprecipitation and proteomic analysis to investigate binding partners for circulating PHB1. Crosslinking of PHB1 to serum resulted in two complexes of approximately 150 and 100 kDa, which contained both PHB1 and fragments of C3. The binding of PHB1 to C3 was confirmed using a solid phase assay where the dissociation constant was approximately 90 fmol/l. PHB1, but not the closely related PHB2, was able to enhance complement activation and induce lysis of sensitized sheep erythrocytes when added with normal serum but not with C3-deficient serum. The ability of PHB1 to bind to, and activate C3 suggests that PHB1 may have a previously unrecognized role in innate immunity.
authors.affiliation: Departments of Physiology & Internal Medicine, University of Manitoba, Winnipeg R3E 0W3, Canada. mishra@cc.umanitoba.ca
authors.forename: Suresh
authors.initials: S
authors.lastname: Mishra
authors.forename: Saby
authors.initials: S
authors.lastname: Moulik
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Murphy
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000737:chemistry* / Q000276:immunology; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D000091402:Prohibitins; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry* / Q000276:immunology; D012756:Sheep
chemical_list: D003176:Complement C3; C000717328:PHB protein, human; C000717331:PHB2 protein, human; D000091402:Prohibitins; D012097:Repressor Proteins