Premium
Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions
Author(s) -
Leone Philippe,
Comoletti Davide,
Ferracci Géraldine,
Conrod Sandrine,
Garcia Simon U,
Taylor Palmer,
Bourne Yves,
Marchot Pascale
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.123
Subject(s) - neuroligin , neurexin , biology , mutant , biophysics , microbiology and biotechnology , biochemistry , gene , receptor , postsynaptic potential
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 Å‐resolution crystal structure of a soluble neurexin‐1β–neuroligin‐4 (Nrx1β–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 Nrx1β binding. Surface plasmon resonance analysis of the binding of structure‐guided Nrx1β mutants towards NL4 and neuroligin‐1 shows that flexibility of the Nrx1β‐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 Nrx1β association, unique conformational reshaping of the NL4 surface is required to permit Nrx1β association.