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| | <StructureSection load='5kwr' size='340' side='right'caption='[[5kwr]], [[Resolution|resolution]] 1.79Å' scene=''> | | <StructureSection load='5kwr' size='340' side='right'caption='[[5kwr]], [[Resolution|resolution]] 1.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kwr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KWR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KWR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kwr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KWR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KWR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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]] 1.795Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cbln1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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://proteopedia.org/fgij/fg.htm?mol=5kwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kwr OCA], [http://pdbe.org/5kwr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kwr RCSB], [http://www.ebi.ac.uk/pdbsum/5kwr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kwr 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=5kwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kwr OCA], [https://pdbe.org/5kwr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kwr RCSB], [https://www.ebi.ac.uk/pdbsum/5kwr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kwr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CBLN1_RAT CBLN1_RAT]] Required for synapse integrity and synaptic plasticity. During cerebellar synapse formation, essential for the formation and maintenance of parallel fiber and Purkinje cell synapses. When parallel fibers make contact with Purkinje spines, CBLN1 interaction with GRID2 triggers the recruitment of NRXN1 and secretory vesicles to the sites of contact. NRXN1-CBLN1-GRID2 signaling induces presynaptic morphological changes, which may further accumulate pre- and postsynaptic components to promote bidirectional maturation of parallel fiber - Purkinje cell functionally active synapses by a positive feedback mechanism. Required for CBLN3 export from the endoplasmic reticulum and secretion (By similarity). The cerebellin exerts neuromodulatory functions. Directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release. A conversion to [des-Ser1]-cerebellin by endopeptidases seems to be required for its autocrine-paracrine regulatory functions.<ref>PMID:10688962</ref> <ref>PMID:15702230</ref> | + | [https://www.uniprot.org/uniprot/CBLN1_RAT CBLN1_RAT] Required for synapse integrity and synaptic plasticity. During cerebellar synapse formation, essential for the formation and maintenance of parallel fiber and Purkinje cell synapses. When parallel fibers make contact with Purkinje spines, CBLN1 interaction with GRID2 triggers the recruitment of NRXN1 and secretory vesicles to the sites of contact. NRXN1-CBLN1-GRID2 signaling induces presynaptic morphological changes, which may further accumulate pre- and postsynaptic components to promote bidirectional maturation of parallel fiber - Purkinje cell functionally active synapses by a positive feedback mechanism. Required for CBLN3 export from the endoplasmic reticulum and secretion (By similarity). The cerebellin exerts neuromodulatory functions. Directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release. A conversion to [des-Ser1]-cerebellin by endopeptidases seems to be required for its autocrine-paracrine regulatory functions.<ref>PMID:10688962</ref> <ref>PMID:15702230</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cheng, S]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Ozkan, E]] | + | [[Category: Cheng S]] |
| - | [[Category: Extracellular protein]] | + | [[Category: Ozkan E]] |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Nervous system]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Synapse protein]]
| + | |
| Structural highlights
Function
CBLN1_RAT Required for synapse integrity and synaptic plasticity. During cerebellar synapse formation, essential for the formation and maintenance of parallel fiber and Purkinje cell synapses. When parallel fibers make contact with Purkinje spines, CBLN1 interaction with GRID2 triggers the recruitment of NRXN1 and secretory vesicles to the sites of contact. NRXN1-CBLN1-GRID2 signaling induces presynaptic morphological changes, which may further accumulate pre- and postsynaptic components to promote bidirectional maturation of parallel fiber - Purkinje cell functionally active synapses by a positive feedback mechanism. Required for CBLN3 export from the endoplasmic reticulum and secretion (By similarity). The cerebellin exerts neuromodulatory functions. Directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release. A conversion to [des-Ser1]-cerebellin by endopeptidases seems to be required for its autocrine-paracrine regulatory functions.[1] [2]
Publication Abstract from PubMed
Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein cerebellin with pre-synaptic neurexin and post-synaptic delta-type glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of alpha- and beta-neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain. In contrast, we show that the interaction of cerebellin with isolated GluD2 ectodomain is low affinity, which is not simply an outcome of lost avidity when compared with binding with a tetrameric full-length receptor. Rather, high-affinity capture of cerebellin by post-synaptic terminals is likely controlled by long-distance regulation within this transsynaptic complex. Altogether, our results suggest unusual conformational flexibility within all components of the complex.
Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex.,Cheng S, Seven AB, Wang J, Skiniotis G, Ozkan E Structure. 2016 Dec 6;24(12):2163-2173. doi: 10.1016/j.str.2016.11.004. PMID:27926833[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Albertin G, Malendowicz LK, Macchi C, Markowska A, Nussdorfer GG. Cerebellin stimulates the secretory activity of the rat adrenal gland: in vitro and in vivo studies. Neuropeptides. 2000 Feb;34(1):7-11. PMID:10688962 doi:http://dx.doi.org/10.1054/npep.1999.0779
- ↑ Rucinski M, Albertin G, Spinazzi R, Ziolkowska A, Nussdorfer GG, Malendowicz LK. Cerebellin in the rat adrenal gland: gene expression and effects of CER and [des-Ser1]CER on the secretion and growth of cultured adrenocortical cells. Int J Mol Med. 2005 Mar;15(3):411-5. PMID:15702230
- ↑ Cheng S, Seven AB, Wang J, Skiniotis G, Ozkan E. Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex. Structure. 2016 Dec 6;24(12):2163-2173. doi: 10.1016/j.str.2016.11.004. PMID:27926833 doi:http://dx.doi.org/10.1016/j.str.2016.11.004
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