The laminin-binding domain of agrin is structurally related to N-TIMP-1

Agrin is the key organizer of postsynaptic differentiation at the neuromusc ular junction. This organization activity requires the binding of agrin to the synaptic basal lamina. Binding is conferred by the N-terminal agrin (Nt A) domain, which mediates a high-affinity interaction with the coiled coil domain of laminins. Here, we report the crystal structure of chicken NtA at 1.6 Angstrom resolution. The structure reveals that NtA harbors an oligosa ccharide/oligonucleotide-binding fold with several possible sites for the i nteraction with different ligands. A high structural similarity of NtA with the protease inhibition domain in tissue inhibitor of metallo-proteinases- 1 (TIMP- 1) supports the idea of additional functions of agrin besides syna ptogenic activity.