Evidence for alternative roles of cholinesterases (ChEs), independent of their catalytic activity, has emerged in recent years. We have identified a functional region common to ChEs and to a set of neural cell adhesion proteins believed to be structurally related to ChEs due to their high sequence similarity, but which lack the active site serine. Quantitative analysis of the electrostatic surface potential at the entrance to the active site gorge of AChE, and in the analogous zone of the ChE-like domain of the adhesion proteins, shows very good correlation. These findings, together with previous evidence involving this same region in a possible cell recognition function for ChEs, led us to define a new family of adhesion proteins which we have named ChE-like adhesion molecules (CLAMs).
We are studying two different CLAMs, i.e. Drosophila neurotactin and gliotactin. Each contains an extracellular ChE-like domain, a transmembrane domain, and a cytoplasmic domain. We are cloning the extracellular and cytoplasmic regions of each separately in E. coli and in Pichia, and plan to purify and crystallize them, and to determine their 3D structures. We also intend to determine the structure of a complex of neurotactin¹s extra-cellular domain, with its adhesion partner, amalgam (which we have also recently cloned and expressed). These studies will permit visualization of the 3D structure of the esterase domain of a novel type of adhesion protein. The cytoplasmic domain of neurotactin does not appear to be similar to any know sequence, so determination of its 3D structure will also be of interest.