The structure of neurexin 1α reveals features promoting a role as synaptic organizer

Structure. 2011 Jun 8;19(6):779-89. doi: 10.1016/j.str.2011.03.012. Epub 2011 May 27.


α-neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The α-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how α-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1α extracellular domain (n1α) to 2.65 Å. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 Å structure of n1α carrying splice insert SS#3 in LNS4 reveals that SS#3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables α-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Calcium / chemistry
  • Cattle
  • Crystallography, X-Ray
  • Glycoproteins / chemistry*
  • Models, Molecular
  • Neuropeptides / chemistry*
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry*
  • Surface Properties
  • Synapses / chemistry*


  • Glycoproteins
  • Neuropeptides
  • Recombinant Proteins
  • neurexophilin
  • Calcium