EPB41L3; A Target Enabling Package

EPB41L3 is, with moesin (MSN), a member of the FERM family, which is highly expressed in brain as well as in other tissues (kidney, intestine, and testis). Similar to MSN, it binds to the C-terminus of CD44 and transmits signals to the cytoskeleton. EPB41L3 is inversely correlated with markers of Alzheimer’s Disease (AD). We have chosen to pursue the EPB41L3-CD44 interaction as a potential key driver in AD, and as a selectivity target for FERM proteins. This TEP includes expression constructs and methods for purification of the FERM domain from recombinant E. coli; Fluorescence-based assays for binding its ligand; a peptide from the cytoplasmic tail of CD44; crystal structures and a soakable crystallization system; and small molecules identified from a crystal-based fragment screen. We have also expressed several related FERM domains which can be used as a selectivity panel when developing new ligands. In follow-up work, we plan to expand the fragment hits to generate chemical tools for both EPB41L3 and moesin.