2xb6 | pdb_00002xb6
REVISITED CRYSTAL STRUCTURE OF NEUREXIN1BETA-NEUROLIGIN4 COMPLEX
Structural highlights
Disease[NLGNX_HUMAN] Defects in NLGN4X may be the cause of susceptibility to autism X-linked type 2 (AUTSX2) [MIM:300495]. AUTSX2 is a pervasive developmental disorder (PDD), prototypically characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age.[1] Defects in NLGN4X may be the cause of susceptibility to X-linked Asperger syndrome 2 (ASPGX2) [MIM:300497]. ASPGX2 is considered to be a form of childhood autism. Function[NLGNX_HUMAN] Putative neuronal cell surface protein involved in cell-cell-interactions. [NRX1B_RAT] Neuronal cell surface protein that may be involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins. May play a role in formation or maintenance of synaptic junctions. May mediate intracellular signaling. May play a role in angiogenesis (By similarity).[2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions.,Leone P, Comoletti D, Ferracci G, Conrod S, Garcia SU, Taylor P, Bourne Y, Marchot P EMBO J. 2010 Jul 21;29(14):2461-71. Epub 2010 Jun 11. PMID:20543817[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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