Abstract
Two crystal structures of Japanin, an 18 kDa immune-modulatory lipocalin from the Brown Ear Tick (Rhipicephalus appendiculatus), have been determined at 2.2 and 2.4 Å resolution. In both crystal forms the protein is in complex with cholesterol, which sits in a closed pocket at the centre of the lipocalin barrel. Both crystal forms are dimers, which are also observed in solution. Molecular modelling suggests that previously-described members of a tick protein family bearing high sequence homology to Japanin are also likely to bind cholesterol or cholesterol derivatives.
Highlights
Hard ticks are obligate haematophagous parasites with an unusually lengthy feeding period for an ectoparasite, during which the tick modulates the host immune response to prevent it mounting an effective anti-parasite response
Japanin is predicted from sequence data to be a lipocalin, a member of a family of ubiquitous small proteins found in both prokaryotes and eukaryotes
The lipocalin family shows a large expansion, with many lipocalins detected in the salivary gland transcriptome and appearing to bind biogenic amines such as histamine, or fatty acids such as leukotrienes, helping control inflammation and aiding blood-feeding[6,7,8]
Summary
Hard ticks are obligate haematophagous parasites with an unusually lengthy feeding period for an ectoparasite (up to 15 days), during which the tick modulates the host immune response to prevent it mounting an effective anti-parasite response. This immunomodulation is mediated by a complex cocktail of compounds, affecting several arms of the immune response[1], including the activation of dendritic cells (DC), a central process in the initiation of adaptive immunity. To provide insight into Japanin’s mechanism of action, we here present two crystal structures of the protein They reveal that Japanin exists in complex with cholesterol and that it forms a dimer, as well as confirming the prediction from primary sequence that it adopts the lipocalin fold[9]. Japanin becomes the first lipocalin for which the molecular details of cholesterol binding are described
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