3B3Q

Crystal structure of a synaptic adhesion complex

Summary for 3B3Q

• Entry DOI: 10.2210/pdb3b3q/pdb
• Descriptor: Nlgn1 protein, NRXN1 protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: synaptic formation, adhesion, heterophilic, protein-protein complex, calcium binding, membrane, transmembrane, cell adhesion
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 4
• Total formula weight: 173737.17

Authors

Chen, X.,Liu, H.,Shim, A.,Focia, P.,He, X. (deposition date: 2007-10-22, release date: 2008-01-15, Last modification date: 2024-10-09)

Primary citation

Chen, X.,Liu, H.,Shim, A.H.,Focia, P.J.,He, X.
Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions.
Nat.Struct.Mol.Biol., 15:50-56, 2008

PubMed Abstract: 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 A between the mouse neuroligin-1 (NL1) cholinesterase-like domain and the mouse neurexin-1beta (NX1beta) 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-NX1beta 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.

PubMed: 18084303
DOI: 10.1038/nsmb1350

Experimental method

X-RAY DIFFRACTION (2.4 Å)