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PDBsum entry 2r1b

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protein metals links
Cell adhesion, splicing PDB id
2r1b
Jmol
Contents
Protein chains
198 a.a. *
Metals
_CA ×2
Waters ×353
* Residue conservation analysis
PDB id:
2r1b
Name: Cell adhesion, splicing
Title: Crystal structure of rat neurexin 1beta with a splice insert
Structure: Neurexin-1-beta. Chain: a, b. Fragment: lns/lg domain. Synonym: neurexin i-beta. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: nrxn1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.72Å     R-factor:   0.200     R-free:   0.225
Authors: G.Rudenko
Key ref:
K.C.Shen et al. (2008). Regulation of neurexin 1beta tertiary structure and ligand binding through alternative splicing. Structure, 16, 422-431. PubMed id: 18334217 DOI: 10.1016/j.str.2008.01.005
Date:
22-Aug-07     Release date:   25-Mar-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q63373  (NRX1B_RAT) -  Neurexin-1-beta
Seq:
Struc:
468 a.a.
198 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/j.str.2008.01.005 Structure 16:422-431 (2008)
PubMed id: 18334217  
 
 
Regulation of neurexin 1beta tertiary structure and ligand binding through alternative splicing.
K.C.Shen, D.A.Kuczynska, I.J.Wu, B.H.Murray, L.R.Sheckler, G.Rudenko.
 
  ABSTRACT  
 
Neurexins and neuroligins play an essential role in synapse function, and their alterations are linked to autistic spectrum disorder. Interactions between neurexins and neuroligins regulate inhibitory and excitatory synaptogenesis in vitro through a "splice-insert signaling code." In particular, neurexin 1beta carrying an alternative splice insert at site SS#4 interacts with neuroligin 2 (found predominantly at inhibitory synapses) but much less so with other neuroligins (those carrying an insert at site B and prevalent at excitatory synapses). The structure of neurexin 1beta+SS#4 reveals dramatic rearrangements to the "hypervariable surface," the binding site for neuroligins. The splice insert protrudes as a long helix into space, triggers conversion of loop beta10-beta11 into a helix rearranging the binding site for neuroligins, and rearranges the Ca(2+)-binding site required for ligand binding, increasing its affinity. Our structures reveal the mechanism by which neurexin 1beta isoforms acquire neuroligin splice isoform selectivity.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Helix Sα1 Adopts a Well-Defined Orientation in the Crystal Structure of n1β_L(30)
(A) Superposition of the crystallographically independent n1β_L(30) molecules A (magenta) and B (yellow) found in the asymmetric unit. The Ca^2+ ion is shown as a blue sphere.
(B) Omit map density for Sα1 in molecule A.
(C) Omit map density for Sα1 in molecule B. (B) and (C) display electron density contoured at 1σ from simulated annealed composite omit maps calculated by CNS (Brunger et al., 1998).
Figure 7.
Figure 7. Splice Insert SS#4 Disrupts the Protein:Protein Interface Seen in the n1β:Neuroligin 1 Complex
(A) Superposition of n1β_L(30) (gray C^α trace) onto n1β (light cyan C^α trace) of the n1β:neuroligin 1 complex (PDB code: 3BIW), with neuroligin 1 shown as a cyan C^α trace. The splice insert residues are in maroon, “switch” residues in yellow (n1β_L(30)) or orange (n1β), respectively.
(B) Close up of the Ca^2+-binding site in n1β_L(30) as docked on n1β of the n1β:neuroligin 1 complex. N1β_L(30) shown in gray and yellow, neuroligin 1 in cyan. Relevant side chains are depicted in ball and stick (carbon, gray, yellow, or cyan; nitrogen, blue; oxygen, red). The Ca^2+ ion is shown as a blue sphere. For the sake of clarity, the side chain Ile^236 of n1β_L(30) and the trace of n1β are not shown. Orange arrows indicate the side chain of Glu^397 and main chain carbonyl of Gln^395 from neuroligin 1 that undergo (water-mediated) interaction with the Ca^2+-binding site of n1β ([Araç et al., 2007] and [Chen et al., 2007]).
 
  The above figures are reprinted from an Open Access publication published by Cell Press: Structure (2008, 16, 422-431) 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.  
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
20213668 R.J.Falconer, A.Penkova, I.Jelesarov, and B.M.Collins (2010).
Survey of the year 2008: applications of isothermal titration calorimetry.
  J Mol Recognit, 23, 395-413.  
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
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.  
18923512 T.C.Südhof (2008).
Neuroligins and neurexins link synaptic function to cognitive disease.
  Nature, 455, 903-911.  
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.