Structure and laminin-binding specificity of the NtA domain expressed in eukaryotic cells

Joseph B. Mascarenhas, Markus A. Rüegg, Takako Sasaki, Johannes A. Eble, Jürgen Engel, Jörg Stetefeld

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11 Scopus citations


Agrin is a key organizer for postsynaptic differentiation at the neuromuscular junction (NMJ). This activity requires the binding of agrin to the synaptic basal lamina via its N-terminal (NtA) domain. It has been suggested that this binding is mediated by conserved amino acids in the γ1 chain of laminin. Here, we report the crystal structure of chicken NtA expressed in eukaryotic HEK293 cells. In contrast to the previously published structure [Stetefeld, J., Jenny, M., Schulthess, T., Landwehr, R., Schumacher, B., Frank, S., Ruegg, M.A., Engel, J., Kammerer, R.A., 2001. The laminin-binding domain of agrin is structurally related to N-TIMP-1. Nat. Struct. Biol., 8, 705-709.], which was derived from the NtA domain expressed in E. coli, the new data show that the N-terminal tail region (amino acid residues Asn1-Arg5) is highly structured. Moreover, the disulfide bridge between Cys2 and Cys74 was also present. In addition, we show that the binding of NtA requires the γ1 chain of laminin and is not greatly affected by the composition of β chains. These results confirm a model of the NtA-laminin complex where conserved amino acids in the γ1 chain are prerequisite for the binding to agrin and they further emphasize that the source of protein can be critical in structure determination.

Original languageEnglish (US)
Pages (from-to)507-513
Number of pages7
JournalMatrix Biology
Issue number8
StatePublished - Jan 2005
Externally publishedYes


  • Agrin
  • Agrin-laminin interaction
  • N-terminal agrin

ASJC Scopus subject areas

  • Molecular Biology


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