Variability and action mechanism of a family of anticomplement proteins in Ixodes ricinus.
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.
Couvreur
Bernard
B
Laboratory for Molecular Biology of Ectoparasites, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, Gosselies, Belgium.
Beaufays
Jérôme
J
Charon
Cédric
C
Lahaye
Kathia
K
Gensale
François
F
Denis
Valérie
V
Charloteaux
Benoît
B
Decrem
Yves
Y
Prévôt
Pierre-Paul
PP
Brossard
Michel
M
Vanhamme
Luc
L
Godfroid
Edmond
E
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
D003169:Complement Inactivator Proteins; D019476:Insect Proteins; D011414:Properdin; D012685:Sepharose