Molecular basis of non-self recognition by the horseshoe crab lectins

The target molecules of innate immunity are not proteins of direct gene products but the molecular arrays or patterns on pathogens, called pathogen-associated molecular patterns (PAMPs). The self/non-self discrimination by innate immunity through simple ligands universally expressed both on pathogens and hosts, such as monosaccharides and the acetyl group, probably depends on the density or clustering patterns of the ligands. The specific recognition by the horseshoe crab lectins, named tachylectins, with a propeller-like fold or a propeller-like oligomeric arrangement is reinforced by the short distance between the individual binding sites that interact with PAMPs. There is virtually no conformational change in the main or side chains of tachylectins upon binding with the ligands. This low structural flexibility of the propeller structures must be very important for specific interaction with PAMPs.