The macromolecular architecture of extracellular domain of αNRXN1: Domain organization, flexibility, and insights into trans-synaptic disposition

Davide Comoletti, Meghan T. Miller, Cy M. Jeffries, Jennifer Wilson, Borries Demeler, Palmer Taylor, Jill Trewhella, Terunaga Nakagawa

Research output: Contribution to journalArticle

26 Scopus citations


Neurexins are multidomain synaptic cell-adhesion proteins that associate with multiple partnering proteins. Genetic evidence indicates that neurexins may contribute to autism, schizophrenia, and nicotine dependence. Using analytical ultracentrifugation, single-particle electron microscopy, and solution X-ray scattering, we obtained a three-dimensional structural model of the entire extracellular domain of neurexin-1α. This protein adopts a dimensionally asymmetric conformation that is monomeric in solution, with a maximum dimension of ∼170 Å. The extracellular domain of α-neurexin maintains a characteristic "Y" shape, whereby LNS domains 1-4 form an extended base of the "Y" and LNS5-6 the shorter arms. Moreover, two major regions of flexibility are present: one between EGF1 and LNS2, corresponding to splice site 1, another between LNS5 and 6. We thus provide the first structural insights into the architecture of the extracellular region of neurexin-1α, show how the protein may fit in the synaptic cleft, and how partnering proteins could bind simultaneously.

Original languageEnglish (US)
Pages (from-to)1044-1053
Number of pages10
Issue number8
StatePublished - Aug 1 2010



  • Molneuro

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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