The crystal structure of the α-neurexin-1 extracellular region reveals a hinge point for mediating synaptic adhesion and function

Meghan T. Miller, Mauro Mileni, Davide Comoletti, Raymond C. Stevens, Michal Harel, Palmer Taylor

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

α- and β-neurexins (NRXNs) are transmembrane cell adhesion proteins that localize to presynaptic membranes in neurons and interact with the postsynaptic neuroligins (NLGNs). Their gene mutations are associated with the autism spectrum disorders. The extracellular region of α-NRXNs, containing nine independently folded domains, has structural complexity and unique functional characteristics, distinguishing it from the smaller β-NRXNs. We have solved the X-ray crystal structure of seven contiguous domains of the α-NRXN-1 extracellular region at 3.0 resolution. The structure reveals an arrangement where the N-terminal five domains adopt a more rigid linear conformation and the two C-terminal domains form a separate arm connected by a flexible hinge. In an extended conformation the molecule is suitably configured to accommodate a bound NLGN molecule, as supported by structural comparison and surface plasmon resonance. These studies provide the structural basis for a multifunctional synaptic adhesion complex mediated by α-NRXN-1.

Original languageEnglish (US)
Pages (from-to)767-778
Number of pages12
JournalStructure
Volume19
Issue number6
DOIs
StatePublished - Jun 8 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Structural Biology

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