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==Crystal structure of agrin and LRP4 complex==
==Crystal structure of agrin and LRP4 complex==
<StructureSection load='3v65' size='340' side='right' caption='[[3v65]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
<StructureSection load='3v65' size='340' side='right'caption='[[3v65]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3v65]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V65 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3v65]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V65 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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3v64|3v64]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3v64|3v64]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Agrn, Agrin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]), Lrp4, Megf7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Agrn, Agrin ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Lrp4, Megf7 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3v65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v65 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3v65 RCSB], [http://www.ebi.ac.uk/pdbsum/3v65 PDBsum]</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=3v65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v65 OCA], [https://pdbe.org/3v65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v65 RCSB], [https://www.ebi.ac.uk/pdbsum/3v65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v65 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/AGRIN_RAT AGRIN_RAT]] Isoform 1: heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. This neuron-specific (z+) isoform is a component of the AGRN-LRP4 receptor complex that induces the phosphorylation and activation of MUSK. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Calcium ions are required for maximal AChR clustering. AGRN function in neurons is highly regulated by alternative splicing, glycan binding and proteolytic processing. Modulates calcium ion homestasis in neurons, specifically by inducing an increase in cytoplasmic calcium ions. Functions differentially in the central nervous system (CNS) by inhibiting the alpha(3)-subtype of Na+/K+-ATPase and evoking depolarization at CNS synapses. This transmembrane agrin (TM-agrin) isoform, the predominate form in neurons of the brain, induces dendritic filopodia and synapse formation in mature hippocampal neurons in large part due to the attached glycosaminoglycan chains and the action of Rho-family GTPases.<ref>PMID:8398142</ref> <ref>PMID:8653787</ref> <ref>PMID:8693000</ref> <ref>PMID:18775496</ref> <ref>PMID:19524020</ref> <ref>PMID:20471381</ref> <ref>PMID:20566625</ref> <ref>PMID:20505824</ref>  Isoform 1, isoform 4, isoform 5 and isoform 6: neuron-specific (z+) isoforms that contain C-terminal insertions of 8-19 AA are potent activators of AChR clustering. Isoform 5, agrin (z+8), containing the 8-AA insert, forms a receptor complex in myotubules containing the neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of the LDL receptor family. The splicing factors, NOVA1 and NOVA2, regulate AGRN splicing and production of the 'z' isoforms.<ref>PMID:8398142</ref> <ref>PMID:8653787</ref> <ref>PMID:8693000</ref> <ref>PMID:18775496</ref> <ref>PMID:19524020</ref> <ref>PMID:20471381</ref> <ref>PMID:20566625</ref> <ref>PMID:20505824</ref>  Agrin N-terminal 110 kDa subunit: is involved in regulation of neurite outgrowth probably due to the presence of the glycosaminoglcan (GAG) side chains of heparan and chondroitin sulfate attached to the Ser/Thr- and Gly/Ser-rich regions. Also involved in modulation of growth factor signaling (By similarity).<ref>PMID:8398142</ref> <ref>PMID:8653787</ref> <ref>PMID:8693000</ref> <ref>PMID:18775496</ref> <ref>PMID:19524020</ref> <ref>PMID:20471381</ref> <ref>PMID:20566625</ref> <ref>PMID:20505824</ref>  Agrin C-terminal 22 kDa fragment: this released fragment is important for agrin signaling and to exert a maximal dendritic filopodia-inducing effect. All 'z' splice variants (z+) of this fragment also show an increase in the number of filopodia.<ref>PMID:8398142</ref> <ref>PMID:8653787</ref> <ref>PMID:8693000</ref> <ref>PMID:18775496</ref> <ref>PMID:19524020</ref> <ref>PMID:20471381</ref> <ref>PMID:20566625</ref> <ref>PMID:20505824</ref>   
[[https://www.uniprot.org/uniprot/AGRIN_RAT AGRIN_RAT]] Isoform 1: heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. This neuron-specific (z+) isoform is a component of the AGRN-LRP4 receptor complex that induces the phosphorylation and activation of MUSK. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Calcium ions are required for maximal AChR clustering. AGRN function in neurons is highly regulated by alternative splicing, glycan binding and proteolytic processing. Modulates calcium ion homestasis in neurons, specifically by inducing an increase in cytoplasmic calcium ions. Functions differentially in the central nervous system (CNS) by inhibiting the alpha(3)-subtype of Na+/K+-ATPase and evoking depolarization at CNS synapses. This transmembrane agrin (TM-agrin) isoform, the predominate form in neurons of the brain, induces dendritic filopodia and synapse formation in mature hippocampal neurons in large part due to the attached glycosaminoglycan chains and the action of Rho-family GTPases.<ref>PMID:8398142</ref> <ref>PMID:8653787</ref> <ref>PMID:8693000</ref> <ref>PMID:18775496</ref> <ref>PMID:19524020</ref> <ref>PMID:20471381</ref> <ref>PMID:20566625</ref> <ref>PMID:20505824</ref>  Isoform 1, isoform 4, isoform 5 and isoform 6: neuron-specific (z+) isoforms that contain C-terminal insertions of 8-19 AA are potent activators of AChR clustering. Isoform 5, agrin (z+8), containing the 8-AA insert, forms a receptor complex in myotubules containing the neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of the LDL receptor family. The splicing factors, NOVA1 and NOVA2, regulate AGRN splicing and production of the 'z' isoforms.<ref>PMID:8398142</ref> <ref>PMID:8653787</ref> <ref>PMID:8693000</ref> <ref>PMID:18775496</ref> <ref>PMID:19524020</ref> <ref>PMID:20471381</ref> <ref>PMID:20566625</ref> <ref>PMID:20505824</ref>  Agrin N-terminal 110 kDa subunit: is involved in regulation of neurite outgrowth probably due to the presence of the glycosaminoglcan (GAG) side chains of heparan and chondroitin sulfate attached to the Ser/Thr- and Gly/Ser-rich regions. Also involved in modulation of growth factor signaling (By similarity).<ref>PMID:8398142</ref> <ref>PMID:8653787</ref> <ref>PMID:8693000</ref> <ref>PMID:18775496</ref> <ref>PMID:19524020</ref> <ref>PMID:20471381</ref> <ref>PMID:20566625</ref> <ref>PMID:20505824</ref>  Agrin C-terminal 22 kDa fragment: this released fragment is important for agrin signaling and to exert a maximal dendritic filopodia-inducing effect. All 'z' splice variants (z+) of this fragment also show an increase in the number of filopodia.<ref>PMID:8398142</ref> <ref>PMID:8653787</ref> <ref>PMID:8693000</ref> <ref>PMID:18775496</ref> <ref>PMID:19524020</ref> <ref>PMID:20471381</ref> <ref>PMID:20566625</ref> <ref>PMID:20505824</ref>  [[https://www.uniprot.org/uniprot/LRP4_RAT LRP4_RAT]] Mediates SOST-dependent inhibition of bone formation (By similarity). Functions as a specific facilitator of SOST-mediated inhibition of Wnt signaling (By similarity). Plays a key role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Directly binds AGRIN and recruits it to the MUSK signaling complex. Mediates the AGRIN-induced phosphorylation of MUSK, the kinase of the complex. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Alternatively, may be involved in the negative regulation of the canonical Wnt signaling pathway, being able to antagonize the LRP6-mediated activation of this pathway. More generally, has been proposed to function as a cell surface endocytic receptor binding and internalizing extracellular ligands for degradation by lysosomes.
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
<div class="pdbe-citations 3v65" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Agrin|Agrin]]
*[[Agrin 3D structures|Agrin 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Rattus norvegicus]]
[[Category: Buffalo rat]]
[[Category: Large Structures]]
[[Category: Jin, R]]
[[Category: Jin, R]]
[[Category: Zong, Y]]
[[Category: Zong, Y]]

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