Agrin is a ~600 kDa extracellular matrix proteoglycan that induces "aggregation" of acetylcholine receptors (AChRs) on the postsynaptic membranes of neuromuscular junctions. The C-terminus of agrin has three laminin-like globular domains, G1-G3. Agrin-G3 is the domain responsible for AChR clustering. Alternative mRNA splicing of the agrin gene results in several isoforms. The 'B' isoforms differ by inserts in the agrin-G3 domain. Isoforms with inserts are specifically expressed in neurons and induce AChR clustering. The solution structure of the B0 isoform of agrin-G3 is shown. NMR studies indicate that both the B0 and the neural B8 isoforms bind calcium. The unique perspective on agrin-G3 provided by NMR is of a domain with a versatile, flexible interaction interface that has its dynamics modulated by calcium and sequence inserts.
Stetefeld J, Alexandrescu AT, Maciejewski MW, Jenny M, Rathgeb-Szabo K, Schulthess T, Landwehr R, Frank S, Ruegg MA, Kammerer RA (2004) Modulation of agrin function by alternative splicing and Ca2+ binding. Structure 12, 503-15.
Alexandrescu AT, Maciejewski MW, Ruegg MA, Engel J, Kammerer RA (2001) 1H, 13C and 15N backbone assignments for the C-terminal globular domain of agrin. J Biomol NMR 20, 295-6.