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| | ==Revisited crystal structure of Neurexin1beta-Neuroligin4 complex== | | ==Revisited crystal structure of Neurexin1beta-Neuroligin4 complex== |
| - | <StructureSection load='2xb6' size='340' side='right' caption='[[2xb6]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='2xb6' size='340' side='right'caption='[[2xb6]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2xb6]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XB6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XB6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2xb6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XB6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XB6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c4r|1c4r]], [[2vh8|2vh8]], [[2wqz|2wqz]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xb6 OCA], [http://pdbe.org/2xb6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xb6 RCSB], [http://www.ebi.ac.uk/pdbsum/2xb6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xb6 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xb6 OCA], [https://pdbe.org/2xb6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xb6 RCSB], [https://www.ebi.ac.uk/pdbsum/2xb6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xb6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/NLGNX_HUMAN NLGNX_HUMAN]] Defects in NLGN4X may be the cause of susceptibility to autism X-linked type 2 (AUTSX2) [MIM:[http://omim.org/entry/300495 300495]]. AUTSX2 is a pervasive developmental disorder (PDD), prototypically characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age.<ref>PMID:12669065</ref> Defects in NLGN4X may be the cause of susceptibility to X-linked Asperger syndrome 2 (ASPGX2) [MIM:[http://omim.org/entry/300497 300497]]. ASPGX2 is considered to be a form of childhood autism. | + | [https://www.uniprot.org/uniprot/NLGNX_HUMAN NLGNX_HUMAN] Defects in NLGN4X may be the cause of susceptibility to autism X-linked type 2 (AUTSX2) [MIM:[https://omim.org/entry/300495 300495]. AUTSX2 is a pervasive developmental disorder (PDD), prototypically characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age.<ref>PMID:12669065</ref> Defects in NLGN4X may be the cause of susceptibility to X-linked Asperger syndrome 2 (ASPGX2) [MIM:[https://omim.org/entry/300497 300497]. ASPGX2 is considered to be a form of childhood autism. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NLGNX_HUMAN NLGNX_HUMAN]] Putative neuronal cell surface protein involved in cell-cell-interactions. [[http://www.uniprot.org/uniprot/NRX1B_RAT NRX1B_RAT]] Neuronal cell surface protein that may be involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins. May play a role in formation or maintenance of synaptic junctions. May mediate intracellular signaling. May play a role in angiogenesis (By similarity).<ref>PMID:9325340</ref> | + | [https://www.uniprot.org/uniprot/NLGNX_HUMAN NLGNX_HUMAN] Putative neuronal cell surface protein involved in cell-cell-interactions. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Bourne, Y]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Comoletti, D]] | + | [[Category: Bourne Y]] |
| - | [[Category: Conrod, S]] | + | [[Category: Comoletti D]] |
| - | [[Category: Ferracci, G]] | + | [[Category: Conrod S]] |
| - | [[Category: Garcia, S U]] | + | [[Category: Ferracci G]] |
| - | [[Category: Leone, P]] | + | [[Category: Garcia SU]] |
| - | [[Category: Marchot, P]] | + | [[Category: Leone P]] |
| - | [[Category: Taylor, P]] | + | [[Category: Marchot P]] |
| - | [[Category: Alpha-beta-hydrolase fold]]
| + | [[Category: Taylor P]] |
| - | [[Category: Autism]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Conformational rearrangement]]
| + | |
| Structural highlights
2xb6 is a 4 chain structure with sequence from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.6Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
NLGNX_HUMAN Defects in NLGN4X may be the cause of susceptibility to autism X-linked type 2 (AUTSX2) [MIM:300495. AUTSX2 is a pervasive developmental disorder (PDD), prototypically characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age.[1] Defects in NLGN4X may be the cause of susceptibility to X-linked Asperger syndrome 2 (ASPGX2) [MIM:300497. ASPGX2 is considered to be a form of childhood autism.
Function
NLGNX_HUMAN Putative neuronal cell surface protein involved in cell-cell-interactions.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The extracellular domains of neuroligins and neurexins interact through Ca(2+) to form flexible trans-synaptic associations characterized by selectivity for neuroligin or neurexin subtypes. This heterophilic interaction, essential for synaptic maturation and differentiation, is regulated by gene selection, alternative mRNA splicing and post-translational modifications. A new, 2.6 A-resolution crystal structure of a soluble neurexin-1beta-neuroligin-4 (Nrx1beta-NL4) complex permits a detailed description of the Ca(2+)-coordinated interface and unveils concerted positional rearrangements of several residues of NL4, not observed in neuroligin-1, associated with Nrx1beta binding. Surface plasmon resonance analysis of the binding of structure-guided Nrx1beta mutants towards NL4 and neuroligin-1 shows that flexibility of the Nrx1beta-binding site in NL4 is reflected in a greater dissociation constant of the complex and higher sensitivity to ionic strength and pH variations. Analysis of neuroligin mutants points to critical functions for two respective residues in neuroligin-1 and neuroligin-2 in governing the affinity of the complexes. Although neuroligin-1 and neuroligin-2 have pre-determined conformations that respectively promote and prevent Nrx1beta association, unique conformational reshaping of the NL4 surface is required to permit Nrx1beta association.
Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions.,Leone P, Comoletti D, Ferracci G, Conrod S, Garcia SU, Taylor P, Bourne Y, Marchot P EMBO J. 2010 Jul 21;29(14):2461-71. Epub 2010 Jun 11. PMID:20543817[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet. 2003 May;34(1):27-9. PMID:12669065 doi:10.1038/ng1136
- ↑ Leone P, Comoletti D, Ferracci G, Conrod S, Garcia SU, Taylor P, Bourne Y, Marchot P. Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions. EMBO J. 2010 Jul 21;29(14):2461-71. Epub 2010 Jun 11. PMID:20543817 doi:10.1038/emboj.2010.123
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