Abstract
Agrin is the key organizer of postsynaptic differentiation at the neuromuscular junction. This organization activity requires the binding of agrin to the synaptic basal lamina. Binding is conferred by the N-terminal agrin (NtA) 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 Å resolution. The structure reveals that NtA harbors an oligosaccharide/oligonucleotide-binding fold with several possible sites for the interaction with different ligands. A high structural similarity of NtA with the protease inhibition domain in tissue inhibitor of metalloproteinases-1 (TIMP-1) supports the idea of additional functions of agrin besides synaptogenic activity.
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Acknowledgements
We thank N.J. Bulleid and G. Orriss for critical reading of the manuscript. This work was supported by the Swiss National Science Foundation to J.E.
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Stetefeld, J., Jenny, M., Schulthess, T. et al. The laminin-binding domain of agrin is structurally related to N-TIMP-1. Nat Struct Mol Biol 8, 705–709 (2001). https://doi.org/10.1038/90422
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DOI: https://doi.org/10.1038/90422
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