Saposin-like proteins (SAPLIPs) from soil-transmitted helminths play pivotal roles in host-pathogen interactions and have a high potential as targets for vaccination against parasitic diseases. We have identified two non-orthologous SAPLIPs from human and dog hookworm, Na-SLP-1 and Ac-SLP-1, and solved their three-dimensional crystal structures. Both proteins share the property of membrane binding as monitored by liposome co-pelleting assays and monolayer adsorption. Neither SAPLIP displayed any significant haemolytic or bactericidal activity. Based on the structural information, as well as the results from monolayer adsorption, we propose models of membrane interactions for both SAPLIPs. Initial membrane contact of the monomeric Na-SLP-1 is most likely by electrostatic interactions between the membrane surface and a prominent basic surface patch. In case of the dimeric Ac-SLP-1, membrane interactions are most likely initiated by a unique tryptophan residue that has previously been implicated in membrane interactions in other SAPLIPs.

The NCS protein Visinin-like Protein 1 (VILIP-1) transduces calcium signals in the brain and serves as an effector of the non-retinal receptor guanylyl cyclases (GCs) GC-A and GC-B, and nicotinic acetyl choline receptors (nAchR). Analysis of the quaternary structure of VILIP-1 in solution reveals the existence of monomeric and dimeric species, the relative contents of which are affected but not exclusively regulated by divalent metal ions and Redox conditions. Using small-angle X-ray scattering, we have investigated the low resolution structure of the calcium-bound VILIP-1 dimer under reducing conditions. Scattering profiles for samples with high monomeric and dimeric contents have been obtained. The dimerization interface involves residues from EF-hand regions EF3 and EF4.Using monolayer adsorption experiments, we show that myristoylated and unmyristoylated VILIP-1 can bind lipid membranes. The presence of calcium only marginally improves binding of the protein to the monolayer, suggesting that charged residues at the protein surface may play a role in the binding process.In the presence of calcium, VILIP-1 undergoes a conformational re-arrangement, exposing previously hidden surfaces for interaction with protein partners. We hypothesise a working model where dimeric VILIP-1 interacts with the membrane where it binds membrane-bound receptors in a calcium-dependent manner.