RGD Reference Report - Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions. - Rat Genome Database

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Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions.

Authors: Leone, P  Comoletti, D  Ferracci, G  Conrod, S  Garcia, SU  Taylor, P  Bourne, Y  Marchot, P 
Citation: Leone P, etal., EMBO J. 2010 Jul 21;29(14):2461-71. doi: 10.1038/emboj.2010.123. Epub 2010 Jun 11.
RGD ID: 8553972
Pubmed: PMID:20543817   (View Abstract at PubMed)
PMCID: PMC2910273   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2010.123   (Journal Full-text)

The extracellular domains of neuroligins and neurexins interact through Ca(2+) to form flexible trans-synaptic associations characterized by selectivity for neuroligin or neurexin subtypes. This heterophilic interaction, essential for synaptic maturation and differentiation, is regulated by gene selection, alternative mRNA splicing and post-translational modifications. A new, 2.6 A-resolution crystal structure of a soluble neurexin-1beta-neuroligin-4 (Nrx1beta-NL4) complex permits a detailed description of the Ca(2+)-coordinated interface and unveils concerted positional rearrangements of several residues of NL4, not observed in neuroligin-1, associated with Nrx1beta binding. Surface plasmon resonance analysis of the binding of structure-guided Nrx1beta mutants towards NL4 and neuroligin-1 shows that flexibility of the Nrx1beta-binding site in NL4 is reflected in a greater dissociation constant of the complex and higher sensitivity to ionic strength and pH variations. Analysis of neuroligin mutants points to critical functions for two respective residues in neuroligin-1 and neuroligin-2 in governing the affinity of the complexes. Although neuroligin-1 and neuroligin-2 have pre-determined conformations that respectively promote and prevent Nrx1beta association, unique conformational reshaping of the NL4 surface is required to permit Nrx1beta association.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nlgn1Ratprotein binding enablesIPIUniProtKB:Q63373-3PMID:20543817IntAct 
Nrxn1Ratprotein binding enablesIPIUniProtKB:Q62765-2PMID:20543817IntAct 
Nrxn1Ratprotein binding enablesIPIUniProtKB:Q8N0W4PMID:20543817IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Nlgn1  (neuroligin 1)
Nrxn1  (neurexin 1)

Additional Information