The laminin-binding domain of agrin is structurally related to N-TIMP-1.
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.
Stetefeld
J
J
Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Jenny
M
M
Schulthess
T
T
Landwehr
R
R
Schumacher
B
B
Frank
S
S
Rüegg
M A
MA
Engel
J
J
Kammerer
R A
RA
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*
D018171:Agrin; D007797:Laminin; D008024:Ligands; D019715:Tissue Inhibitor of Metalloproteinase-1