title: Variability and action mechanism of a family of anticomplement proteins in Ixodes ricinus.
abstract: BACKGROUND
  Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families.
  
  
  RESULTS
  We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in Ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical or functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity.
  
  
  CONCLUSIONS
  Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway. Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods.
authors.affiliation: Laboratory for Molecular Biology of Ectoparasites, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Couvreur
authors.forename: Jérôme
authors.initials: J
authors.lastname: Beaufays
authors.forename: Cédric
authors.initials: C
authors.lastname: Charon
authors.forename: Kathia
authors.initials: K
authors.lastname: Lahaye
authors.forename: François
authors.initials: F
authors.lastname: Gensale
authors.forename: Valérie
authors.initials: V
authors.lastname: Denis
authors.forename: Benoît
authors.initials: B
authors.lastname: Charloteaux
authors.forename: Yves
authors.initials: Y
authors.lastname: Decrem
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Prévôt
authors.forename: Michel
authors.initials: M
authors.lastname: Brossard
authors.forename: Luc
authors.initials: L
authors.lastname: Vanhamme
authors.forename: Edmond
authors.initials: E
authors.lastname: Godfroid
mesh_terms: D000818:Animals; D003169:Complement Inactivator Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D019476:Insect Proteins / Q000145:classification / Q000378:metabolism*; D018884:Ixodes / Q000378:metabolism*; D010802:Phylogeny; D011414:Properdin / Q000378:metabolism; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012685:Sepharose
chemical_list: D003169:Complement Inactivator Proteins; D019476:Insect Proteins; D011414:Properdin; D012685:Sepharose