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| | ==Structure of rat Nogo receptor bound to 1D9 antagonist antibody== | | ==Structure of rat Nogo receptor bound to 1D9 antagonist antibody== |
| - | <StructureSection load='3kj4' size='340' side='right' caption='[[3kj4]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='3kj4' size='340' side='right'caption='[[3kj4]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3kj4]] is a 6 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=3KJ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KJ4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3kj4]] is a 6 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=3KJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KJ4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ozn|1ozn]], [[1p8t|1p8t]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nogo Receptor, Nogor, Rtn4r ([http://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'>[https://proteopedia.org/fgij/fg.htm?mol=3kj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kj4 OCA], [https://pdbe.org/3kj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kj4 RCSB], [https://www.ebi.ac.uk/pdbsum/3kj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kj4 ProSAT]</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=3kj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kj4 OCA], [http://pdbe.org/3kj4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kj4 RCSB], [http://www.ebi.ac.uk/pdbsum/3kj4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kj4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RTN4R_RAT RTN4R_RAT]] Receptor for RTN4, OMG and MAG. Mediates axonal growth inhibition and may play a role in regulating axonal regeneration and plasticity in the adult central nervous system. Acts in conjunction with RTN4 and LIGO1 in regulating neuronal precursor cell motility during cortical development (By similarity). | + | [https://www.uniprot.org/uniprot/RTN4R_RAT RTN4R_RAT] Receptor for RTN4, OMG and MAG. Mediates axonal growth inhibition and may play a role in regulating axonal regeneration and plasticity in the adult central nervous system. Acts in conjunction with RTN4 and LIGO1 in regulating neuronal precursor cell motility during cortical development (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Silvian, L F]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Cell membrane]] | + | [[Category: Silvian LF]] |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Gpi-anchor]]
| + | |
| - | [[Category: Immune system]]
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| - | [[Category: Leucine-rich repeat]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Lrr]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Nogo receptor antagonist antibody]]
| + | |
| - | [[Category: Receptor]]
| + | |
| Structural highlights
Function
RTN4R_RAT Receptor for RTN4, OMG and MAG. Mediates axonal growth inhibition and may play a role in regulating axonal regeneration and plasticity in the adult central nervous system. Acts in conjunction with RTN4 and LIGO1 in regulating neuronal precursor cell motility during cortical development (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Nogo-66 receptor (NgR1) is part of a signaling complex that inhibits axon regeneration in the CNS. Truncated soluble versions of NgR1 have been used successfully to promote axon regeneration in animal models of spinal cord injury, raising interest in this protein as a potential therapeutic target. The leucine-rich repeat (LRR) regions in NgR1 are flanked by N- and C-terminal disulfide-containing "cap" domains (LRRNT and LRRCT, respectively). In this work we show that, although functionally active, the NgR1(310)-Fc fusion protein contains mislinked and heterogeneous disulfide patterns in the LRRCT, and we report the generation of a series of variant molecules specifically designed to prevent this heterogeneity. Using these variants we explored the effects of modifying the NgR1 truncation site or the spacing between the NgR1 and Fc domains, or replacing cysteines within the NgR1 or IgG hinge regions. One variant, which incorporates subsititutions of Cys266 and Cys309 with alanines, completely eliminated disulfide scrambling, while maintaining functional in vitro and in vivo efficacy. This modified NgR1-Fc molecule represents a significantly improved candidate for further pharmaceutical development, and may serve as a useful model for the optimization of other IgG fusion proteins made from LRR proteins.
Resolution of disulfide heterogeneity in Nogo receptor 1 fusion proteins by molecular engineering.,Weinreb PH, Wen D, Qian F, Wildes CP, Garber EA, Walus L, Jung MY, Wang J, Relton JK, Amatucci J, Wang R, Porreca F, Silvian L, Meier W, Pepinsky RB, Lee DH Biotechnol Appl Biochem. 2010 Sep 3. PMID:20815818[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Weinreb PH, Wen D, Qian F, Wildes CP, Garber EA, Walus L, Jung MY, Wang J, Relton JK, Amatucci J, Wang R, Porreca F, Silvian L, Meier W, Pepinsky RB, Lee DH. Resolution of disulfide heterogeneity in Nogo receptor 1 fusion proteins by molecular engineering. Biotechnol Appl Biochem. 2010 Sep 3. PMID:20815818 doi:10.1042/BA20100061
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