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| | ==Crystal structure of the Cbln1 C1q domain trimer in complex with the amino-terminal domain (ATD) of iGluR Delta-2 (GluD2)== | | ==Crystal structure of the Cbln1 C1q domain trimer in complex with the amino-terminal domain (ATD) of iGluR Delta-2 (GluD2)== |
| - | <StructureSection load='5kca' size='340' side='right' caption='[[5kca]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='5kca' size='340' side='right'caption='[[5kca]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kca]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KCA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kca]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KCA 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></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]] 3.1Å</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=5kca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kca OCA], [http://pdbe.org/5kca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kca RCSB], [http://www.ebi.ac.uk/pdbsum/5kca PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kca ProSAT]</span></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></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=5kca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kca OCA], [https://pdbe.org/5kca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kca RCSB], [https://www.ebi.ac.uk/pdbsum/5kca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kca ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/GRID2_HUMAN GRID2_HUMAN] Autosomal recessive congenital cerebellar ataxia due to GRID2 deficiency. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CBLN1_HUMAN CBLN1_HUMAN]] 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 peptide 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 (By similarity). | + | [https://www.uniprot.org/uniprot/GRID2_HUMAN GRID2_HUMAN] Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.[https://www.uniprot.org/uniprot/CBLN1_HUMAN CBLN1_HUMAN] 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 peptide 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 (By similarity). |
| | <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: Aricescu, A R]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Elegheert, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Cerebellin]] | + | [[Category: Aricescu AR]] |
| - | [[Category: Neurotransmission]] | + | [[Category: Elegheert J]] |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Disease
GRID2_HUMAN Autosomal recessive congenital cerebellar ataxia due to GRID2 deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
GRID2_HUMAN Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.CBLN1_HUMAN 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 peptide 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 (By similarity).
Publication Abstract from PubMed
Ionotropic glutamate receptor (iGluR) family members are integrated into supramolecular complexes that modulate their location and function at excitatory synapses. However, a lack of structural information beyond isolated receptors or fragments thereof currently limits the mechanistic understanding of physiological iGluR signaling. Here, we report structural and functional analyses of the prototypical molecular bridge linking postsynaptic iGluR delta2 (GluD2) and presynaptic beta-neurexin 1 (beta-NRX1) via Cbln1, a C1q-like synaptic organizer. We show how Cbln1 hexamers "anchor" GluD2 amino-terminal domain dimers to monomeric beta-NRX1. This arrangement promotes synaptogenesis and is essential for D: -serine-dependent GluD2 signaling in vivo, which underlies long-term depression of cerebellar parallel fiber-Purkinje cell (PF-PC) synapses and motor coordination in developing mice. These results lead to a model where protein and small-molecule ligands synergistically control synaptic iGluR function.
Structural basis for integration of GluD receptors within synaptic organizer complexes.,Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR Science. 2016 Jul 15;353(6296):295-9. doi: 10.1126/science.aae0104. PMID:27418511[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR. Structural basis for integration of GluD receptors within synaptic organizer complexes. Science. 2016 Jul 15;353(6296):295-9. doi: 10.1126/science.aae0104. PMID:27418511 doi:http://dx.doi.org/10.1126/science.aae0104
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