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| | ==Deglycosylated Nogo Receptor with native disulfide structure== | | ==Deglycosylated Nogo Receptor with native disulfide structure== |
| - | <StructureSection load='5o0k' size='340' side='right' caption='[[5o0k]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='5o0k' size='340' side='right'caption='[[5o0k]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5o0k]] is a 2 chain structure with sequence from [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=5O0K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O0K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5o0k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O0K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O0K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rtn4r, Ngr1, Nogor ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5o0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o0k OCA], [http://pdbe.org/5o0k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o0k RCSB], [http://www.ebi.ac.uk/pdbsum/5o0k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o0k 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=5o0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o0k OCA], [https://pdbe.org/5o0k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o0k RCSB], [https://www.ebi.ac.uk/pdbsum/5o0k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o0k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RTN4R_MOUSE RTN4R_MOUSE]] Receptor for RTN4, OMG and MAG (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:18411262, PubMed:22923615). Functions as receptor for the sialylated gangliosides GT1b and GM1 (PubMed:18411262). Besides, functions as receptor for chondroitin sulfate proteoglycans (PubMed:22406547). Can also bind heparin (PubMed:22406547). Intracellular signaling cascades are triggered via the coreceptor NGFR (By similarity). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200). Mediates axonal growth inhibition (By similarity). Mediates axonal growth inhibition and plays a role in regulating axon regeneration and neuronal plasticity in the adult central nervous system (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:22923615). Plays a role in postnatal brain development (PubMed:27339102). Required for normal axon migration across the brain midline and normal formation of the corpus callosum (PubMed:27339102). Protects motoneurons against apoptosis; protection against apoptosis is probably mediated via interaction with MAG (PubMed:26335717). Acts in conjunction with RTN4 and LINGO1 in regulating neuronal precursor cell motility during cortical development (PubMed:20093372). Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200).[UniProtKB:Q9BZR6]<ref>PMID:11201742</ref> <ref>PMID:12089450</ref> <ref>PMID:15504325</ref> <ref>PMID:20093372</ref> <ref>PMID:22325200</ref> <ref>PMID:22406547</ref> <ref>PMID:22923615</ref> <ref>PMID:26335717</ref> <ref>PMID:27339102</ref> | + | [https://www.uniprot.org/uniprot/RTN4R_MOUSE RTN4R_MOUSE] Receptor for RTN4, OMG and MAG (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:18411262, PubMed:22923615). Functions as receptor for the sialylated gangliosides GT1b and GM1 (PubMed:18411262). Besides, functions as receptor for chondroitin sulfate proteoglycans (PubMed:22406547). Can also bind heparin (PubMed:22406547). Intracellular signaling cascades are triggered via the coreceptor NGFR (By similarity). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200). Mediates axonal growth inhibition (By similarity). Mediates axonal growth inhibition and plays a role in regulating axon regeneration and neuronal plasticity in the adult central nervous system (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:22923615). Plays a role in postnatal brain development (PubMed:27339102). Required for normal axon migration across the brain midline and normal formation of the corpus callosum (PubMed:27339102). Protects motoneurons against apoptosis; protection against apoptosis is probably mediated via interaction with MAG (PubMed:26335717). Acts in conjunction with RTN4 and LINGO1 in regulating neuronal precursor cell motility during cortical development (PubMed:20093372). Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200).[UniProtKB:Q9BZR6]<ref>PMID:11201742</ref> <ref>PMID:12089450</ref> <ref>PMID:15504325</ref> <ref>PMID:20093372</ref> <ref>PMID:22325200</ref> <ref>PMID:22406547</ref> <ref>PMID:22923615</ref> <ref>PMID:26335717</ref> <ref>PMID:27339102</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The Nogo Receptor (NgR) is a glycophosphatidylinositol-anchored cell-surface protein and is a receptor for three myelin-associated inhibitors of regeneration: myelin-associated glycoprotein, Nogo66 and oligodendrocyte myelin glycoprotein. In combination with different co-receptors, NgR mediates signalling that reduces neuronal plasticity. The available structures of the NgR ligand-binding leucine-rich repeat (LRR) domain have an artificial disulfide pattern owing to truncated C-terminal construct boundaries. NgR has previously been shown to self-associate via its LRR domain, but the structural basis of this interaction remains elusive. Here, crystal structures of the NgR LRR with a longer C-terminal segment and a native disulfide pattern are presented. An additional C-terminal loop proximal to the C-terminal LRR cap is stabilized by two newly formed disulfide bonds, but is otherwise mostly unstructured in the absence of any stabilizing interactions. NgR crystallized in six unique crystal forms, three of which share a crystal-packing interface. NgR crystal-packing interfaces from all eight unique crystal forms are compared in order to explore how NgR could self-interact on the neuronal plasma membrane. |
| | + | |
| | + | Nogo Receptor crystal structures with a native disulfide pattern suggest a novel mode of self-interaction.,Pronker MF, Tas RP, Vlieg HC, Janssen BJC Acta Crystallogr D Struct Biol. 2017 Nov 1;73(Pt 11):860-876. doi:, 10.1107/S2059798317013791. Epub 2017 Oct 19. PMID:29095159<ref>PMID:29095159</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 5o0k" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Janssen, B J.C]] | + | [[Category: Mus musculus]] |
| - | [[Category: Pronker, M F]] | + | [[Category: Janssen BJC]] |
| - | [[Category: Disulfide structure]] | + | [[Category: Pronker MF]] |
| - | [[Category: Leucine-rich repeat domain]]
| + | |
| - | [[Category: Nervous system]]
| + | |
| - | [[Category: Signaling]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
RTN4R_MOUSE Receptor for RTN4, OMG and MAG (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:18411262, PubMed:22923615). Functions as receptor for the sialylated gangliosides GT1b and GM1 (PubMed:18411262). Besides, functions as receptor for chondroitin sulfate proteoglycans (PubMed:22406547). Can also bind heparin (PubMed:22406547). Intracellular signaling cascades are triggered via the coreceptor NGFR (By similarity). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200). Mediates axonal growth inhibition (By similarity). Mediates axonal growth inhibition and plays a role in regulating axon regeneration and neuronal plasticity in the adult central nervous system (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:22923615). Plays a role in postnatal brain development (PubMed:27339102). Required for normal axon migration across the brain midline and normal formation of the corpus callosum (PubMed:27339102). Protects motoneurons against apoptosis; protection against apoptosis is probably mediated via interaction with MAG (PubMed:26335717). Acts in conjunction with RTN4 and LINGO1 in regulating neuronal precursor cell motility during cortical development (PubMed:20093372). Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200).[UniProtKB:Q9BZR6][1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
The Nogo Receptor (NgR) is a glycophosphatidylinositol-anchored cell-surface protein and is a receptor for three myelin-associated inhibitors of regeneration: myelin-associated glycoprotein, Nogo66 and oligodendrocyte myelin glycoprotein. In combination with different co-receptors, NgR mediates signalling that reduces neuronal plasticity. The available structures of the NgR ligand-binding leucine-rich repeat (LRR) domain have an artificial disulfide pattern owing to truncated C-terminal construct boundaries. NgR has previously been shown to self-associate via its LRR domain, but the structural basis of this interaction remains elusive. Here, crystal structures of the NgR LRR with a longer C-terminal segment and a native disulfide pattern are presented. An additional C-terminal loop proximal to the C-terminal LRR cap is stabilized by two newly formed disulfide bonds, but is otherwise mostly unstructured in the absence of any stabilizing interactions. NgR crystallized in six unique crystal forms, three of which share a crystal-packing interface. NgR crystal-packing interfaces from all eight unique crystal forms are compared in order to explore how NgR could self-interact on the neuronal plasma membrane.
Nogo Receptor crystal structures with a native disulfide pattern suggest a novel mode of self-interaction.,Pronker MF, Tas RP, Vlieg HC, Janssen BJC Acta Crystallogr D Struct Biol. 2017 Nov 1;73(Pt 11):860-876. doi:, 10.1107/S2059798317013791. Epub 2017 Oct 19. PMID:29095159[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature. 2001 Jan 18;409(6818):341-6. PMID:11201742 doi:http://dx.doi.org/10.1038/35053072
- ↑ Liu BP, Fournier A, GrandPre T, Strittmatter SM. Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor. Science. 2002 Aug 16;297(5584):1190-3. Epub 2002 Jun 27. PMID:12089450 doi:http://dx.doi.org/10.1126/science.1073031
- ↑ Kim JE, Liu BP, Park JH, Strittmatter SM. Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury. Neuron. 2004 Oct 28;44(3):439-51. PMID:15504325 doi:http://dx.doi.org/10.1016/j.neuron.2004.10.015
- ↑ Mathis C, Schroter A, Thallmair M, Schwab ME. Nogo-a regulates neural precursor migration in the embryonic mouse cortex. Cereb Cortex. 2010 Oct;20(10):2380-90. doi: 10.1093/cercor/bhp307. Epub 2010 Jan , 21. PMID:20093372 doi:http://dx.doi.org/10.1093/cercor/bhp307
- ↑ Wills ZP, Mandel-Brehm C, Mardinly AR, McCord AE, Giger RJ, Greenberg ME. The nogo receptor family restricts synapse number in the developing hippocampus. Neuron. 2012 Feb 9;73(3):466-81. doi: 10.1016/j.neuron.2011.11.029. PMID:22325200 doi:http://dx.doi.org/10.1016/j.neuron.2011.11.029
- ↑ Dickendesher TL, Baldwin KT, Mironova YA, Koriyama Y, Raiker SJ, Askew KL, Wood A, Geoffroy CG, Zheng B, Liepmann CD, Katagiri Y, Benowitz LI, Geller HM, Giger RJ. NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci. 2012 Mar 11;15(5):703-12. doi: 10.1038/nn.3070. PMID:22406547 doi:http://dx.doi.org/10.1038/nn.3070
- ↑ Nakaya N, Sultana A, Lee HS, Tomarev SI. Olfactomedin 1 interacts with the Nogo A receptor complex to regulate axon growth. J Biol Chem. 2012 Oct 26;287(44):37171-84. doi: 10.1074/jbc.M112.389916. Epub, 2012 Aug 24. PMID:22923615 doi:http://dx.doi.org/10.1074/jbc.M112.389916
- ↑ Palandri A, Salvador VR, Wojnacki J, Vivinetto AL, Schnaar RL, Lopez PH. Myelin-associated glycoprotein modulates apoptosis of motoneurons during early postnatal development via NgR/p75(NTR) receptor-mediated activation of RhoA signaling pathways. Cell Death Dis. 2015 Sep 3;6:e1876. doi: 10.1038/cddis.2015.228. PMID:26335717 doi:http://dx.doi.org/10.1038/cddis.2015.228
- ↑ Yoo SW, Motari MG, Schnaar RL. Agenesis of the corpus callosum in Nogo receptor deficient mice. J Comp Neurol. 2017 Feb 1;525(2):291-301. doi: 10.1002/cne.24064. Epub 2016 Jul, 8. PMID:27339102 doi:http://dx.doi.org/10.1002/cne.24064
- ↑ Pronker MF, Tas RP, Vlieg HC, Janssen BJC. Nogo Receptor crystal structures with a native disulfide pattern suggest a novel mode of self-interaction. Acta Crystallogr D Struct Biol. 2017 Nov 1;73(Pt 11):860-876. doi:, 10.1107/S2059798317013791. Epub 2017 Oct 19. PMID:29095159 doi:http://dx.doi.org/10.1107/S2059798317013791
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