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

Abstract : 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.
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Contributor : Corinne Dumonceaud Connect in order to contact the contributor
Submitted on : Wednesday, September 21, 2011 - 12:22:39 PM
Last modification on : Thursday, January 13, 2022 - 2:20:34 PM

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Philippe Leone, Davide Comoletti, Géraldine Ferracci, Sandrine Conrod, Simon U Garcia, et al.. Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions.. EMBO Journal, EMBO Press, 2010, 29 (14), pp.2461-71. ⟨10.1038/emboj.2010.123⟩. ⟨hal-00625337⟩



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