Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions

Xiaoyan Chen, Heli Liu, Ann H.R. Shim, Pamela J. Focia, Xiaolin He*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


The heterophilic synaptic adhesion molecules neuroligins and neurexins are essential for establishing and maintaining neuronal circuits by modulating the formation and maturation of synapses. The neuroligin-neurexin adhesion is Ca2+-dependent and regulated by alternative splicing. We report a structure of the complex at a resolution of 2.4 Å between the mouse neuroligin-1 (NL1) cholinesterase-like domain and the mouse neurexin-1β (NX1β) LNS (laminin, neurexin and sex hormone-binding globulin-like) domain. The structure revealed a delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated and solvent-supplemented interface, rendering it capable of being modulated by alternative splicing and other regulatory factors. Thermodynamic data supported a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at the edge of the NL1-NX1β interface. Mapping neuroligin mutations implicated in autism indicated that most such mutations are structurally destabilizing, supporting deficient neuroligin biosynthesis and processing as a common cause for this brain disorder.

Original languageEnglish (US)
Pages (from-to)50-56
Number of pages7
JournalNature Structural and Molecular Biology
Issue number1
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology


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