The polyprotein lipid binding proteins of nematodes.

The nematode polyprotein allergens/antigens (NPAs) are specific to nematodes, and are synthesised as tandemly repetitive polypeptides comprising 10 or more repeated units. The polyproteins are post-translationally cleaved at consensus sites to yield multiple copies of the approximately 15-kDa NPA units. These units can be highly diverse in their amino acid sequences, but absolutely conserved signature amino acid positions are identifiable. NPA units are helix-rich and possibly fold as four helix bundle proteins. The NPA units have relatively non-specific lipid binding activities, binding fatty acids and retinoids, with dissociation constants similar to those of lipid transport proteins of vertebrates. Fluorescence-based analysis has indicated that, like most lipid transport proteins, the ligand is taken into the binding site in its entirety, but the binding site environment is unusual. NPAs are synthesised in the gut of nematodes, and presumably act to distribute small lipids from the gut, via the pseudocoelomic fluid, to consuming tissues (muscles, gonads, etc.). In some species, one of the units has a histidine-rich extension peptide which binds haems and certain divalent metal ions. NPAs appear to be released by parasitic nematodes, and may thereby be involved in modification of the local inflammatory and immunological environment of the tissues they inhabit by delivering or sequestering pharmacologically active lipids - they are known to bind arachidonic acids and some of its metabolites, lysophospholipids, and retinoids. NPAs are the only known lipid binding protein made as polyproteins, and are exceptions to the rule that repetitive polyproteins are only produced by cells undergoing programmed cell death and producing specialist products.