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PDBsum entry 3b3q

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protein ligands metals Protein-protein interface(s) links
Cell adhesion PDB id
3b3q
Jmol
Contents
Protein chains
536 a.a. *
187 a.a. *
Ligands
NAG-NAG ×3
NAG
Metals
_CA ×2
Waters ×1552
* Residue conservation analysis
PDB id:
3b3q
Name: Cell adhesion
Title: Crystal structure of a synaptic adhesion complex
Structure: Nlgn1 protein. Chain: a, b. Fragment: cholinesterase-like domain. Engineered: yes. Mutation: yes. Nrxn1 protein. Chain: e, f. Fragment: lns domain or lg domain. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: nlgn1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Homo sapiens. Human. Organism_taxid: 9606.
Resolution:
2.40Å     R-factor:   0.242     R-free:   0.261
Authors: X.Chen,H.Liu,A.Shim,P.Focia,X.He
Key ref:
X.Chen et al. (2008). Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions. Nat Struct Biol, 15, 50-56. PubMed id: 18084303 DOI: 10.1038/nsmb1350
Date:
22-Oct-07     Release date:   15-Jan-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q99K10  (NLGN1_MOUSE) -  Neuroligin-1
Seq:
Struc:
 
Seq:
Struc:
843 a.a.
536 a.a.*
Protein chains
Pfam   ArchSchema ?
P58400  (NRX1B_HUMAN) -  Neurexin-1-beta
Seq:
Struc:
442 a.a.
187 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     positive regulation of synapse maturation   6 terms 

 

 
DOI no: 10.1038/nsmb1350 Nat Struct Biol 15:50-56 (2008)
PubMed id: 18084303  
 
 
Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions.
X.Chen, H.Liu, A.H.Shim, P.J.Focia, X.He.
 
  ABSTRACT  
 
The heterophilic synaptic adhesion molecules neuroligins and neurexins are essential for establishing and maintaining neuronal circuits by modulating the formation and maturation of synapses. The neuroligin-neurexin adhesion is Ca2+-dependent and regulated by alternative splicing. We report a structure of the complex at a resolution of 2.4 A between the mouse neuroligin-1 (NL1) cholinesterase-like domain and the mouse neurexin-1beta (NX1beta) LNS (laminin, neurexin and sex hormone-binding globulin-like) domain. The structure revealed a delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated and solvent-supplemented interface, rendering it capable of being modulated by alternative splicing and other regulatory factors. Thermodynamic data supported a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at the edge of the NL1-NX1beta interface. Mapping neuroligin mutations implicated in autism indicated that most such mutations are structurally destabilizing, supporting deficient neuroligin biosynthesis and processing as a common cause for this brain disorder.
 
  Selected figure(s)  
 
Figure 1.
(a) His-tag pull-down assay showing effects of mutagenesis of NX1 surface residues on NL1 binding.
Figure 5.
The mutated residues, NL1 Asp106 (corresponding to the NL4 G99S mutation), NL1 Lys414 (corresponding to the NL4 K378R mutation), NL1 Arg473 (corresponding to the NL3 R451C mutation) and NL1 Val439 (corresponding to the NL4 V403M mutation), are colored green and shown in space-filling representation, and are mapped on the NL1–NX1 complex (ribbons). These residues are away from the binding and dimerization interfaces, and are mostly buried.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2008, 15, 50-56) copyright 2008.  
  Figures were selected by an automated process.  

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.  
20120026 D.A.Jacques, and J.Trewhella (2010).
Small-angle scattering for structural biology--expanding the frontier while avoiding the pitfalls.
  Protein Sci, 19, 642-657.  
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.  
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.  
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.