The Crystal Structure of the α-Neurexin-1 Extracellular Region Reveals a Hinge Point for Mediating Synaptic Adhesion and Function

Abrahams, 2008, Advances in autism genetics: on the threshold of a new neurobiology, Nat. Rev. Genet., 9, 341, 10.1038/nrg2346 Arac, 2007, Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca2+ interactions, Neuron, 56, 992, 10.1016/j.neuron.2007.12.002 Boucard, 2005, A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins, Neuron, 48, 229, 10.1016/j.neuron.2005.08.026 1994, The CCP4 suite: programs for protein crystallography, Acta Crystallogr. D Biol. Crystallogr., 50, 760, 10.1107/S0907444994003112 Chen, 2008, Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions, Nat. Struct. Mol. Biol., 15, 50, 10.1038/nsmb1350 Chen, 2010, MolProbity: all-atom structure validation for macromolecular crystallography, Acta Crystallogr. D Biol. Crystallogr., 66, 12, 10.1107/S0907444909042073 Cheng, 2009, Presynaptic targeting of alpha4beta 2 nicotinic acetylcholine receptors is regulated by neurexin-1beta, J. Biol. Chem., 284, 23251, 10.1074/jbc.M109.017384 Chenna, 2003, Multiple sequence alignment with the Clustal series of programs, Nucleic Acids Res., 31, 3497, 10.1093/nar/gkg500 Chih, 2006, Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex, Neuron, 51, 171, 10.1016/j.neuron.2006.06.005 Comoletti, 2003, Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1beta, J. Biol. Chem., 278, 50497, 10.1074/jbc.M306803200 Comoletti, 2004, The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing, J. Neurosci., 24, 4889, 10.1523/JNEUROSCI.0468-04.2004 Comoletti, 2006, Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for beta-neurexins, Biochemistry, 45, 12816, 10.1021/bi0614131 Comoletti, 2007, Synaptic arrangement of the neuroligin/beta-neurexin complex revealed by X-ray and neutron scattering, Structure, 15, 693, 10.1016/j.str.2007.04.010 Comoletti, 2010, The macromolecular architecture of extracellular domain of alphaNRXN1: domain organization, flexibility, and insights into trans-synaptic disposition, Structure, 18, 1044, 10.1016/j.str.2010.06.005 Craig, 2006, How to build a central synapse: clues from cell culture, Trends Neurosci., 29, 8, 10.1016/j.tins.2005.11.002 Davletov, 1995, High affinity binding of alpha-latrotoxin to recombinant neurexin I alpha, J. Biol. Chem., 270, 23903, 10.1074/jbc.270.41.23903 de Wit, 2009, LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation, Neuron, 64, 799, 10.1016/j.neuron.2009.12.019 Emsley, 2004, Coot: model-building tools for molecular graphics, Acta Crystallogr. D Biol. Crystallogr., 60, 2126, 10.1107/S0907444904019158 Fabrichny, 2007, Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion, Neuron, 56, 979, 10.1016/j.neuron.2007.11.013 Feng, 2006, High frequency of neurexin 1beta signal peptide structural variants in patients with autism, Neurosci. Lett., 409, 10, 10.1016/j.neulet.2006.08.017 Glessner, 2009, Autism genome-wide copy number variation reveals ubiquitin and neuronal genes, Nature, 459, 569, 10.1038/nature07953 Graf, 2004, Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins, Cell, 119, 1013, 10.1016/j.cell.2004.11.035 Graf, 2006, Structure function and splice site analysis of the synaptogenic activity of the neurexin-1 beta LNS domain, J. Neurosci., 26, 4256, 10.1523/JNEUROSCI.1253-05.2006 Haines, 2003, Glycosylation regulates Notch signalling, Nat. Rev. Mol. Cell Biol., 4, 786, 10.1038/nrm1228 Harris, 1993, O-linked fucose and other post-translational modifications unique to EGF modules, Glycobiology, 3, 219, 10.1093/glycob/3.3.219 Hooft, 1996, Errors in protein structures, Nature, 381, 272, 10.1038/381272a0 Ichtchenko, 1995, Neuroligin 1: a splice site-specific ligand for beta-neurexins, Cell, 81, 435, 10.1016/0092-8674(95)90396-8 Ichtchenko, 1996, Structures, alternative splicing, and neurexin binding of multiple neuroligins, J. Biol. Chem., 271, 2676, 10.1074/jbc.271.5.2676 Kabsch, 1993, Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants, J. Appl. Crystallogr., 26, 795, 10.1107/S0021889893005588 Kang, 2008, Induction of GABAergic postsynaptic differentiation by alpha-neurexins, J. Biol. Chem., 283, 2323, 10.1074/jbc.M703957200 Kim, 2008, Disruption of neurexin 1 associated with autism spectrum disorder, Am. J. Hum. Genet., 82, 199, 10.1016/j.ajhg.2007.09.011 Ko, 2009, LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation, Neuron, 64, 791, 10.1016/j.neuron.2009.12.012 Koehnke, 2008, Crystal structures of beta-neurexin 1 and beta-neurexin 2 ectodomains and dynamics of splice insertion sequence 4, Structure, 16, 410, 10.1016/j.str.2007.12.024 Koehnke, 2010, Splice form dependence of beta-neurexin/neuroligin binding interactions, Neuron, 67, 61, 10.1016/j.neuron.2010.06.001 Krissinel, 2007, Inference of macromolecular assemblies from crystalline state, J. Mol. Biol., 372, 774, 10.1016/j.jmb.2007.05.022 Leone, 2010, Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions, EMBO J., 29, 2461, 10.1038/emboj.2010.123 McCoy, 2007, Phaser crystallographic software, J. Appl. Crystallogr., 40, 658, 10.1107/S0021889807021206 Merry, 2003, O-glycan sialylation and the structure of the stalk-like region of the T cell co-receptor CD8, J. Biol. Chem., 278, 27119, 10.1074/jbc.M213056200 Missler, 1998, Neurexophilin binding to alpha-neurexins. A single LNS domain functions as an independently folding ligand-binding unit, J. Biol. Chem., 273, 34716, 10.1074/jbc.273.52.34716 Missler, 2003, Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis, Nature, 423, 939, 10.1038/nature01755 Moloney, 2000, Fringe is a glycosyltransferase that modifies Notch, Nature, 406, 369, 10.1038/35019000 Myszka, 1999, Improving biosensor analysis, J. Mol. Recognit., 12, 279, 10.1002/(SICI)1099-1352(199909/10)12:5<279::AID-JMR473>3.0.CO;2-3 Okajima, 2008, Biological functions of glycosyltransferase genes involved in O-fucose glycan synthesis, J. Biochem., 144, 1, 10.1093/jb/mvn016 Reissner, 2008, Mutational analysis of the neurexin/neuroligin complex reveals essential and regulatory components, Proc. Natl. Acad. Sci. USA, 105, 15124, 10.1073/pnas.0801639105 Rich, 2001, BIACORE J: a new platform for routine biomolecular interaction analysis, J. Mol. Recognit., 14, 223, 10.1002/jmr.535 Rini, 1995, Lectin structure, Annu. Rev. Biophys. Biomol. Struct., 24, 551, 10.1146/annurev.bb.24.060195.003003 Rudenko, 1999, The structure of the ligand-binding domain of neurexin Ibeta: regulation of LNS domain function by alternative splicing, Cell, 99, 93, 10.1016/S0092-8674(00)80065-3 Rujescu, 2009, Disruption of the neurexin 1 gene is associated with schizophrenia, Hum. Mol. Genet., 18, 988, 10.1093/hmg/ddn351 Sebat, 2007, Strong association of de novo copy number mutations with autism, Science, 316, 445, 10.1126/science.1138659 Sheckler, 2006, Crystal structure of the second LNS/LG domain from neurexin 1alpha: Ca2+ binding and the effects of alternative splicing, J. Biol. Chem., 281, 22896, 10.1074/jbc.M603464200 Shen, 2008, Regulation of neurexin 1beta tertiary structure and ligand binding through alternative splicing, Structure, 16, 422, 10.1016/j.str.2008.01.005 Song, 1999, Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses, Proc. Natl. Acad. Sci. USA, 96, 1100, 10.1073/pnas.96.3.1100 Sudhof, 2001, alpha-Latrotoxin and its receptors: neurexins and CIRL/latrophilins, Annu. Rev. Neurosci., 24, 933, 10.1146/annurev.neuro.24.1.933 Sugita, 2001, A stoichiometric complex of neurexins and dystroglycan in brain, J. Cell Biol., 154, 435, 10.1083/jcb.200105003 Szatmari, 2007, Mapping autism risk loci using genetic linkage and chromosomal rearrangements, Nat. Genet., 39, 319, 10.1038/ng1985 Tabuchi, 2002, Structure and evolution of neurexin genes: insight into the mechanism of alternative splicing, Genomics, 79, 849, 10.1006/geno.2002.6780 Talebizadeh, 2006, Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism, J. Med. Genet., 43, e21, 10.1136/jmg.2005.036897 Theobald, 2006, THESEUS: maximum likelihood superpositioning and analysis of macromolecular structures, Bioinformatics, 22, 2171, 10.1093/bioinformatics/btl332 Ullrich, 1995, Cartography of neurexins: more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons, Neuron, 14, 497, 10.1016/0896-6273(95)90306-2 Ushkaryov, 1992, Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin, Science, 257, 50, 10.1126/science.1621094 Varoqueaux, 2004, Neuroligin 2 is exclusively localized to inhibitory synapses, Eur. J. Cell Biol., 83, 449, 10.1078/0171-9335-00410 Yan, 2008, Neurexin 1alpha structural variants associated with autism, Neurosci. Lett., 438, 368, 10.1016/j.neulet.2008.04.074 Yan, 2005, Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients, Mol. Psychiatry, 10, 329, 10.1038/sj.mp.4001629 Zahir, 2008, A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha, J. Med. Genet., 45, 239, 10.1136/jmg.2007.054437 Zhang, 2010, Neurexins physically and functionally interact with GABA(A) receptors, Neuron, 66, 403, 10.1016/j.neuron.2010.04.008 Zhang, 2005, Extracellular domains of alpha-neurexins participate in regulating synaptic transmission by selectively affecting N- and P/Q-type Ca2+ channels, J. Neurosci., 25, 4330, 10.1523/JNEUROSCI.0497-05.2005 Zweier, 2009, CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila, Am. J. Hum. Genet., 85, 655, 10.1016/j.ajhg.2009.10.004