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protein ligands metals Protein-protein interface(s) links
Cell adhesion PDB id
2wqz
Jmol
Contents
Protein chains
545 a.a. *
177 a.a. *
Ligands
5AX ×2
Metals
_CA ×2
* Residue conservation analysis
PDB id:
2wqz
Name: Cell adhesion
Title: Crystal structure of synaptic protein neuroligin-4 in complex with neurexin-beta 1: alternative refinement
Structure: Neuroligin 4, x-linked. Chain: a, b. Fragment: acetylcholinesterase-like domain, residues 43-619 synonym: neuroligin x, hnlx, neuroligin 4. Engineered: yes. Neurexin-1-beta. Chain: c, d. Fragment: lns domain, residues 80-258. Synonym: neurexin i-beta, beta-neurexin 1.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293. Rattus norvegicus. Norway rat. Organism_taxid: 10116.
Resolution:
3.90Å     R-factor:   0.208     R-free:   0.276
Authors: I.P.Fabrichny,P.Leone,G.Sulzenbacher,D.Comoletti,M.T.Miller, Y.Bourne,P.Marchot
Key ref: I.P.Fabrichny et al. (2007). Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion. Neuron, 56, 979-991. PubMed id: 18093521 DOI: 10.1016/j.neuron.2007.11.013
Date:
28-Aug-09     Release date:   08-Sep-09    
Supersedes: 2vh8
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q8N0W4  (NLGNX_HUMAN) -  Neuroligin-4, X-linked
Seq:
Struc: 		 
Seq:
Struc: 		816 a.a.
545 a.a.*
Protein chains
Pfam   ArchSchema ?
Q63373  (NRX1B_RAT) -  Neurexin-1-beta
Seq:
Struc: 		468 a.a.
177 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     cell adhesion   1 term 

 

 
DOI no: 10.1016/j.neuron.2007.11.013 Neuron 56:979-991 (2007)
PubMed id: 18093521  
 
 
Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion.
I.P.Fabrichny, P.Leone, G.Sulzenbacher, D.Comoletti, M.T.Miller, P.Taylor, Y.Bourne, P.Marchot.
 
  ABSTRACT  
 
The neuroligins are postsynaptic cell adhesion proteins whose associations with presynaptic neurexins participate in synaptogenesis. Mutations in the neuroligin and neurexin genes appear to be associated with autism and mental retardation. The crystal structure of a neuroligin reveals features not found in its catalytically active relatives, such as the fully hydrophobic interface forming the functional neuroligin dimer; the conformations of surface loops surrounding the vestigial active center; the location of determinants that are critical for folding and processing; and the absence of a macromolecular dipole and presence of an electronegative, hydrophilic surface for neurexin binding. The structure of a beta-neurexin-neuroligin complex reveals the precise orientation of the bound neurexin and, despite a limited resolution, provides substantial information on the Ca2+-dependent interactions network involved in trans-synaptic neurexin-neuroligin association. These structures exemplify how an alpha/beta-hydrolase fold varies in surface topography to confer adhesion properties and provide templates for analyzing abnormal processing or recognition events associated with autism.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21155806 G.J.Wright, and P.Washbourne (2011).
Neurexins, neuroligins and LRRTMs: synaptic adhesion getting fishy.
  J Neurochem, 117, 765-778.  
20853446 H.Zhao, S.Xiao, X.Kong, J.Wang, X.Cao, W.Gencheng, H.H.Loh, and P.Y.Law (2011).
Neuron-glial cell communication in the traumatic stress-induced immunomodulation.
  Synapse, 65, 433-440.  
21410790 K.Matsuda, and M.Yuzaki (2011).
Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions.
  Eur J Neurosci, 33, 1447-1461.  
21342763 M.Yuzaki (2011).
Cbln1 and its family proteins in synapse formation and maintenance.
  Curr Opin Neurobiol, 21, 215-220.  
21287623 R.C.Mitra, Z.Zhang, and E.Alexov (2011).
In silico modeling of pH-optimum of protein-protein binding.
  Proteins, 79, 925-936.  
21423409 R.M.Smith, and W.Sadee (2011).
Synaptic signaling and aberrant RNA splicing in autism spectrum disorders.
  Front Synaptic Neurosci, 3, 1.  
21532576 S.L.Shipman, E.Schnell, T.Hirai, B.S.Chen, K.W.Roche, and R.A.Nicoll (2011).
Functional dependence of neuroligin on a new non-PDZ intracellular domain.
  Nat Neurosci, 14, 718-726.  
20034102 A.Rissone, L.Sangiorgio, M.Monopoli, M.Beltrame, I.Zucchi, F.Bussolino, M.Arese, and F.Cotelli (2010).
Characterization of the neuroligin gene family expression and evolution in zebrafish.
  Dev Dyn, 239, 688-702.  
20696403 D.Comoletti, M.T.Miller, C.M.Jeffries, J.Wilson, B.Demeler, P.Taylor, J.Trewhella, and T.Nakagawa (2010).
The macromolecular architecture of extracellular domain of alphaNRXN1: domain organization, flexibility, and insights into trans-synaptic disposition.
  Structure, 18, 1044-1053.  
20543817 P.Leone, D.Comoletti, G.Ferracci, S.Conrod, S.U.Garcia, P.Taylor, Y.Bourne, and P.Marchot (2010).
Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions.
  EMBO J, 29, 2461-2471.
PDB code: 2xb6
20519524 T.J.Siddiqui, R.Pancaroglu, Y.Kang, A.Rooyakkers, and A.M.Craig (2010).
LRRTMs and neuroligins bind neurexins with a differential code to cooperate in glutamate synapse development.
  J Neurosci, 30, 7495-7506.  
19553699 F.Carafoli, N.J.Clout, and E.Hohenester (2009).
Crystal structure of the LG1-3 region of the laminin alpha2 chain.
  J Biol Chem, 284, 22786-22792.
PDB code: 2wjs
19730411 J.Ko, C.Zhang, D.Arac, A.A.Boucard, A.T.Brunger, and T.C.Südhof (2009).
Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation.
  EMBO J, 28, 3244-3255.  
19258455 T.Kuroyanagi, M.Yokoyama, and T.Hirano (2009).
Postsynaptic glutamate receptor delta family contributes to presynaptic terminal differentiation and establishment of synaptic transmission.
  Proc Natl Acad Sci U S A, 106, 4912-4916.  
18812509 C.Reissner, M.Klose, R.Fairless, and M.Missler (2008).
Mutational analysis of the neurexin/neuroligin complex reveals essential and regulatory components.
  Proc Natl Acad Sci U S A, 105, 15124-15129.  
18334217 K.C.Shen, D.A.Kuczynska, I.J.Wu, B.H.Murray, L.R.Sheckler, and G.Rudenko (2008).
Regulation of neurexin 1beta tertiary structure and ligand binding through alternative splicing.
  Structure, 16, 422-431.
PDB codes: 2r16 2r1b 2r1d
18434543 M.F.Bolliger, J.Pei, S.Maxeiner, A.A.Boucard, N.V.Grishin, and T.C.Südhof (2008).
Unusually rapid evolution of Neuroligin-4 in mice.
  Proc Natl Acad Sci U S A, 105, 6421-6426.  
18974885 S.Biswas, R.J.Russell, C.J.Jackson, M.Vidovic, O.Ganeshina, J.G.Oakeshott, and C.Claudianos (2008).
Bridging the synaptic gap: neuroligins and neurexin I in Apis mellifera.
  PLoS ONE, 3, e3542.  
18923512 T.C.Südhof (2008).
Neuroligins and neurexins link synaptic function to cognitive disease.
  Nature, 455, 903-911.  
18093514 J.N.Levinson, and A.El-Husseini (2007).
A crystal-clear interaction: relating neuroligin/neurexin complex structure to function at the synapse.
  Neuron, 56, 937-939.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.