title: The laminin-binding domain of agrin is structurally related to N-TIMP-1.
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 A 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.
authors.affiliation: Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Stetefeld
authors.forename: M
authors.initials: M
authors.lastname: Jenny
authors.forename: T
authors.initials: T
authors.lastname: Schulthess
authors.forename: R
authors.initials: R
authors.lastname: Landwehr
authors.forename: B
authors.initials: B
authors.lastname: Schumacher
authors.forename: S
authors.initials: S
authors.lastname: Frank
authors.forename: M A
authors.initials: MA
authors.lastname: Rüegg
authors.forename: J
authors.initials: J
authors.lastname: Engel
authors.forename: R A
authors.initials: RA
authors.lastname: Kammerer
mesh_terms: D018171:Agrin / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002645:Chickens; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D055672:Static Electricity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000737:chemistry*
chemical_list: D018171:Agrin; D007797:Laminin; D008024:Ligands; D019715:Tissue Inhibitor of Metalloproteinase-1