The conjuction of a conserved electrostatic motif and a common cholinesterase fold defines a class of adhesion proteins

Abstract

The concept of an electrostatic motif on the surface of biological macromolecules as a definite topographical pattern of electrostatic potentials in 3D space, provides a powerful tool for identification of functionally important regions on the surface of structurally related macromolecules. We employ this tool to analyze the electrostatic properties of cholinesterases (ChEs) from various species and show that all these structures reveal a negative external surface potential in an “annular” area around the entrance to the active-site gorge that becomes more negative as one approaches the rim of the gorge. These potentials are highly correlated among the structures examined, down to a sequence identity as low as 35%, indicating that they are a conserved property of the cholinesterase family. We further suggest that the coincidence between a shared topological arrangement of the macromolecular chain and a conserved electrostatic motif can be used to identify proteins sharing a common recognition mechanism. Using this approach, we identify a functional region common to ChEs and to gliotactin (GLI), neurotactin (NRT), and neuroligin-1 (NL-1), a set of neural cell-adhesion proteins which have been suggested to be structurally related to ChEs due to their high sequence similarity, but lacking the key catalytically active serine.