Electron microscopic structure of agrin and mapping of its binding site in laminin-1

EMBO J. 1998 Jan 15;17(2):335-43. doi: 10.1093/emboj/17.2.335.

Abstract

Agrin is a large, multidomain heparan sulfate proteoglycan that is associated with basement membranes of several tissues. Particular splice variants of agrin are essential for the formation of synaptic structures at the neuromuscular junction. The binding of agrin to laminin appears to be required for its localization to synaptic basal lamina and other basement membranes. Here, electron microscopy was used to determine the structure of agrin and to localize its binding site in laminin-1. Agrin appears as an approximately 95 nm long particle that consists of a globular, N-terminal laminin-binding domain, a central rod predominantly formed by the follistatin-like domains and three globular, C-terminal laminin G-like domains. In a few cases, heparan sulfate glycosaminoglycan chains were seen emerging from the central portion of the core protein. Moreover, we show that agrin binds to the central region of the three-stranded, coiled-coil oligomerization domain in the long arm of laminin-1, which mediates subunit assembly of the native laminin molecule. In summary, our data show for the first time a protein-protein interaction of the extracellular matrix that involves a coiled-coil domain, and they assign a novel role to this domain of laminin-1. Based on this, we propose that agrin associates with basal lamina in a polarized way.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agrin / chemistry*
  • Agrin / genetics
  • Agrin / metabolism
  • Agrin / ultrastructure*
  • Animals
  • Binding Sites
  • COS Cells
  • Cell Line
  • Chickens
  • Humans
  • Laminin / chemistry
  • Laminin / metabolism*
  • Laminin / ultrastructure
  • Microscopy, Electron
  • Peptide Fragments / isolation & purification
  • Peptide Fragments / metabolism
  • Protein Structure, Tertiary
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / ultrastructure

Substances

  • Agrin
  • Laminin
  • Peptide Fragments
  • Recombinant Proteins