Modulation of agrin function by alternative splicing and Ca2+ binding

Structure. 2004 Mar;12(3):503-15. doi: 10.1016/j.str.2004.02.001.


The aggregation of acetylcholine receptors on postsynaptic membranes is a key step in neuromuscular junction development. This process depends on alternatively spliced forms of the proteoglycan agrin with "B-inserts" of 8, 11, or 19 residues in the protein's globular C-terminal domain, G3. Structures of the neural B8 and B11 forms of agrin-G3 were determined by X-ray crystallography. The structure of G3-B0, which lacks inserts, was determined by NMR. The agrin-G3 domain adopts a beta jellyroll fold. The B insert site is flanked by four loops on one edge of the beta sandwich. The loops form a surface that corresponds to a versatile interaction interface in the family of structurally related LNS proteins. NMR and X-ray data indicate that this interaction interface is flexible in agrin-G3 and that flexibility is reduced by Ca(2+) binding. The plasticity of the interaction interface could enable different splice forms of agrin to select between multiple binding partners.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Agrin / genetics*
  • Agrin / metabolism*
  • Alternative Splicing / physiology*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Rats
  • Sequence Alignment


  • Agrin
  • Calcium

Associated data

  • PDB/1PZ7
  • PDB/1PZ8
  • PDB/1PZ9
  • PDB/1Q56