PDBsum entry 2h0b

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protein ligands metals Protein-protein interface(s) links
Cell adhesion PDB id
Protein chains
181 a.a. *
GOL ×4
_CA ×4
Waters ×444
* Residue conservation analysis
PDB id:
Name: Cell adhesion
Title: Crystal structure of the second lns/lg domain from neurexin
Structure: Neurexin-1-alpha. Chain: a, b, c, d. Fragment: second lns/lg domain (residues 295-476). Synonym: neurexin i-alpha. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Gene: nrxn1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.10Å     R-factor:   0.186     R-free:   0.233
Authors: L.R.Sheckler,L.Henry,S.Sugita,T.C.Sudhof,G.Rudenko
Key ref:
L.R.Sheckler et al. (2006). Crystal structure of the second LNS/LG domain from neurexin 1alpha: Ca2+ binding and the effects of alternative splicing. J Biol Chem, 281, 22896-22905. PubMed id: 16772286 DOI: 10.1074/jbc.M603464200
14-May-06     Release date:   20-Jun-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q28146  (NRX1A_BOVIN) -  Neurexin-1
1530 a.a.
181 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     positive regulation of synapse maturation   5 terms 


DOI no: 10.1074/jbc.M603464200 J Biol Chem 281:22896-22905 (2006)
PubMed id: 16772286  
Crystal structure of the second LNS/LG domain from neurexin 1alpha: Ca2+ binding and the effects of alternative splicing.
L.R.Sheckler, L.Henry, S.Sugita, T.C.Südhof, G.Rudenko.
Neurexins mediate protein interactions at the synapse, playing an essential role in synaptic function. Extracellular domains of neurexins, and their fragments, bind a distinct profile of different proteins regulated by alternative splicing and Ca2+. The crystal structure of n1alpha_LNS#2 (the second LNS/LG domain of bovine neurexin 1alpha) reveals large structural differences compared with n1alpha_LNS#6 (or n1beta_LNS), the only other LNS/LG domain for which a structure has been determined. The differences overlap the so-called hyper-variable surface, the putative protein interaction surface that is reshaped as a result of alternative splicing. A Ca2+-binding site is revealed at the center of the hyper-variable surface next to splice insertion sites. Isothermal titration calorimetry indicates that the Ca2+-binding site in n1alpha_LNS#2 has low affinity (Kd approximately 400 microm). Ca2+ binding ceases to be measurable when an 8- or 15-residue splice insert is present at the splice site SS#2 indicating that alternative splicing can affect Ca2+-binding sites of neurexin LNS/LG domains. Our studies initiate a framework for the putative protein interaction sites of neurexin LNS/LG domains. This framework is essential to understand how incorporation of alternative splice inserts expands the information from a limited set of neurexin genes to produce a large array of synaptic adhesion molecules with potentially very different synaptic function.
  Selected figure(s)  
Figure 2.
FIGURE 2. Ribbon diagram of n1 _LNS#2. The -sandwich is shown in a face view (left) and side view (right). -Strands are depicted as yellow arrows, the single -helix is shown in magenta, and the Ca^2+ ion as a blue sphere. The N and C termini of the polypeptide chain are indicated with N and C, respectively.
Figure 4.
FIGURE 4. Ca^2^+-binding site in n1 _LNS#2. The SigmaA-weighted electron density 2m|F[o]| - D|F[c]| contoured at 1.2 and the atomic model are shown depicting the Ca^2+-binding site found at the hyper-variable surface of n1 LNS#2. Dotted lines indicate the interaction network between amino acid residues and solvent molecules chelating the Ca^2+ ion. The binding site in Mol2 is depicted (see Table 2).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 22896-22905) copyright 2006.  
  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.  
20550567 A.M.Thomson, and J.N.Jovanovic (2010).
Mechanisms underlying synapse-specific clustering of GABA(A) receptors.
  Eur J Neurosci, 31, 2193-2203.  
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
  18945720 D.Rujescu, A.Ingason, S.Cichon, O.P.Pietiläinen, M.R.Barnes, T.Toulopoulou, M.Picchioni, E.Vassos, U.Ettinger, E.Bramon, R.Murray, M.Ruggeri, S.Tosato, C.Bonetto, S.Steinberg, E.Sigurdsson, T.Sigmundsson, H.Petursson, A.Gylfason, P.I.Olason, G.Hardarsson, G.A.Jonsdottir, O.Gustafsson, R.Fossdal, I.Giegling, H.J.Möller, A.M.Hartmann, P.Hoffmann, C.Crombie, G.Fraser, N.Walker, J.Lonnqvist, J.Suvisaari, A.Tuulio-Henriksson, S.Djurovic, I.Melle, O.A.Andreassen, T.Hansen, T.Werge, L.A.Kiemeney, B.Franke, J.Veltman, J.E.Buizer-Voskamp, C.Sabatti, R.A.Ophoff, M.Rietschel, M.M.Nöthen, K.Stefansson, L.Peltonen, D.St Clair, H.Stefansson, D.A.Collier, R.S.Kahn, D.Linszen, J.van Os, D.Wiersma, R.Bruggeman, W.Cahn, Haan, L.Krabbendam, and I.Myin-Germeys (2009).
Disruption of the neurexin 1 gene is associated with schizophrenia.
  Hum Mol Genet, 18, 988-996.  
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.  
18550038 D.Comoletti, A.Grishaev, A.E.Whitten, P.Taylor, and J.Trewhella (2008).
Characterization of the solution structure of a neuroligin/beta-neurexin complex.
  Chem Biol Interact, 175, 150-155.  
18250328 J.Koehnke, X.Jin, E.C.Budreck, S.Posy, P.Scheiffele, B.Honig, and L.Shapiro (2008).
Crystal structure of the extracellular cholinesterase-like domain from neuroligin-2.
  Proc Natl Acad Sci U S A, 105, 1873-1878.
PDB code: 3bl8
18334216 J.Koehnke, X.Jin, N.Trbovic, P.S.Katsamba, J.Brasch, G.Ahlsen, P.Scheiffele, B.Honig, A.G.Palmer, and L.Shapiro (2008).
Crystal structures of beta-neurexin 1 and beta-neurexin 2 ectodomains and dynamics of splice insertion sequence 4.
  Structure, 16, 410-421.
PDB codes: 3bod 3bop
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
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
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.  
18084303 X.Chen, H.Liu, A.H.Shim, P.J.Focia, and X.He (2008).
Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions.
  Nat Struct Mol Biol, 15, 50-56.
PDB code: 3b3q
17275284 A.M.Craig, and Y.Kang (2007).
Neurexin-neuroligin signaling in synapse development.
  Curr Opin Neurobiol, 17, 43-52.  
18093522 D.Araç, A.A.Boucard, E.Ozkan, P.Strop, E.Newell, T.C.Südhof, and A.T.Brunger (2007).
Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca2+ interactions.
  Neuron, 56, 992.
PDB codes: 3biw 3bix
17562316 D.Comoletti, A.Grishaev, A.E.Whitten, I.Tsigelny, P.Taylor, and J.Trewhella (2007).
Synaptic arrangement of the neuroligin/beta-neurexin complex revealed by X-ray and neutron scattering.
  Structure, 15, 693-705.  
18093521 I.P.Fabrichny, P.Leone, G.Sulzenbacher, D.Comoletti, M.T.Miller, P.Taylor, Y.Bourne, and P.Marchot (2007).
Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion.
  Neuron, 56, 979-991.
PDB codes: 2vh8 2wqz 3be8
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.