A high affinity serotonin‐ and histamine‐binding lipocalin from tick saliva

Abstract To overcome the inflammatory response in its host, the cattle‐feeding, brown ear tick secretes histamine‐binding proteins into the feeding site. These proteins are β‐barrels with two internal binding sites: a high‐affinity ( H ) site for histamine and a site ( L ) for which the natural ligand is unknown. Here we report a related protein (SHBP), secreted by a rodent‐ and cattle‐feeding tick, that traps both histamine and serotonin. The histamine‐binding H site is well conserved in SHBP, whereas residue changes in the L ‐like site are consistent with binding of the bulkier serotonin molecule. As histamine is a key inflammatory mediator in cattle, while serotonin takes on this role in rodents, the diversification of these tick proteins may reflect host adaptation.