Microbes Bind Complement Inhibitor Factor H via a Common Site

• DOI: 10.1371/journal.ppat.1003308
• Publication Date: 2013-04-18T21:03:12Z
• Authors: T. Meri; H. Amdahl; M. J. Lehtinen; S. Hyvärinen; J. V. McDowell; A. Bhattacharjee; S. Meri; R. Marconi; A. Goldman; T. S. Jokiranta
• Keywords: Complement control protein

To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm innate immunity, alternative pathway complement. It can attack all kinds targets is tightly controlled in plasma on cells by complement regulator factor H (FH). FH binds simultaneously cell surface structures such as heparin or glycosaminoglycans via domain 20 main opsonin C3b 19. Many pathogenic protect themselves from recruiting FH. We analyzed how why different bind domains 19–20 (FH19-20). used a selection FH19-20 point mutants reveal binding sites several microbial proteins whole (Haemophilus influenzae, Bordetella pertussis, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Borrelia burgdorferi, hermsii). show that studied use same region located side 20. Binding was inhibited with showing common site overlaps needed for efficient cells. Surprisingly, enhanced down-regulation activation. this caused formation tripartite complex between protein, FH, C3b. In study we seven representing phyla utilize evasion. not only mimics cells, but also enhances function surfaces novel mechanism formation. This unique example convergent evolution resulting immune evasion pathogens utilization “superevasion site.”