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| | ==The crystal structure of Arc N-lobe complexed with CAMK2A fragment== | | ==The crystal structure of Arc N-lobe complexed with CAMK2A fragment== |
| - | <StructureSection load='4x3i' size='340' side='right' caption='[[4x3i]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4x3i' size='340' side='right'caption='[[4x3i]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4x3i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X3I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4x3i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=4X3I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X3I FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x3h|4x3h]], [[4x3x|4x3x]]</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=4x3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x3i OCA], [https://pdbe.org/4x3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x3i RCSB], [https://www.ebi.ac.uk/pdbsum/4x3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x3i ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Arc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), CAMK2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Calcium/calmodulin-dependent_protein_kinase Calcium/calmodulin-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.17 2.7.11.17] </span></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=4x3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x3i OCA], [http://pdbe.org/4x3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x3i RCSB], [http://www.ebi.ac.uk/pdbsum/4x3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x3i ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ARC_RAT ARC_RAT]] Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics and cell migration (By similarity). Required for consolidation of synaptic plasticity as well as formation of long-term memory. Regulates endocytosis of AMPA receptors in response to synaptic activity. Required for homeostatic synaptic scaling of AMPA receptors.<ref>PMID:17088212</ref> <ref>PMID:17088213</ref> | + | [https://www.uniprot.org/uniprot/ARC_RAT ARC_RAT] Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics and cell migration (By similarity). Required for consolidation of synaptic plasticity as well as formation of long-term memory. Regulates endocytosis of AMPA receptors in response to synaptic activity. Required for homeostatic synaptic scaling of AMPA receptors.<ref>PMID:17088212</ref> <ref>PMID:17088213</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: Calcium/calmodulin-dependent protein kinase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Leahy, D]] | + | [[Category: Leahy D]] |
| - | [[Category: Ward, M]] | + | [[Category: Ward M]] |
| - | [[Category: Worley, P]] | + | [[Category: Worley P]] |
| - | [[Category: Zhang, W]] | + | [[Category: Zhang W]] |
| - | [[Category: Endocytosis mediator]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
ARC_RAT Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics and cell migration (By similarity). Required for consolidation of synaptic plasticity as well as formation of long-term memory. Regulates endocytosis of AMPA receptors in response to synaptic activity. Required for homeostatic synaptic scaling of AMPA receptors.[1] [2]
Publication Abstract from PubMed
Arc is a cellular immediate-early gene (IEG) that functions at excitatory synapses and is required for learning and memory. We report crystal structures of Arc subdomains that form a bi-lobar architecture remarkably similar to the capsid domain of human immunodeficiency virus (HIV) gag protein. Analysis indicates Arc originated from the Ty3/Gypsy retrotransposon family and was "domesticated" in higher vertebrates for synaptic functions. The Arc N-terminal lobe evolved a unique hydrophobic pocket that mediates intermolecular binding with synaptic proteins as resolved in complexes with TARPgamma2 (Stargazin) and CaMKII peptides and is essential for Arc's synaptic function. A consensus sequence for Arc binding identifies several additional partners that include genes implicated in schizophrenia. Arc N-lobe binding is inhibited by small chemicals suggesting Arc's synaptic action may be druggable. These studies reveal the remarkable evolutionary origin of Arc and provide a structural basis for understanding Arc's contribution to neural plasticity and disease.
Structural basis of arc binding to synaptic proteins: implications for cognitive disease.,Zhang W, Wu J, Ward MD, Yang S, Chuang YA, Xiao M, Li R, Leahy DJ, Worley PF Neuron. 2015 Apr 22;86(2):490-500. doi: 10.1016/j.neuron.2015.03.030. Epub 2015, Apr 9. PMID:25864631[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rial Verde EM, Lee-Osbourne J, Worley PF, Malinow R, Cline HT. Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission. Neuron. 2006 Nov 9;52(3):461-74. PMID:17088212 doi:http://dx.doi.org/10.1016/j.neuron.2006.09.031
- ↑ Shepherd JD, Rumbaugh G, Wu J, Chowdhury S, Plath N, Kuhl D, Huganir RL, Worley PF. Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors. Neuron. 2006 Nov 9;52(3):475-84. PMID:17088213 doi:http://dx.doi.org/S0896-6273(06)00683-0
- ↑ Zhang W, Wu J, Ward MD, Yang S, Chuang YA, Xiao M, Li R, Leahy DJ, Worley PF. Structural basis of arc binding to synaptic proteins: implications for cognitive disease. Neuron. 2015 Apr 22;86(2):490-500. doi: 10.1016/j.neuron.2015.03.030. Epub 2015, Apr 9. PMID:25864631 doi:http://dx.doi.org/10.1016/j.neuron.2015.03.030
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