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6fk6

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==Crystal structure of N2C/D282C stabilized opsin bound to RS01==
==Crystal structure of N2C/D282C stabilized opsin bound to RS01==
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<StructureSection load='6fk6' size='340' side='right' caption='[[6fk6]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
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<StructureSection load='6fk6' size='340' side='right'caption='[[6fk6]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6fk6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FK6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FK6 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6fk6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FK6 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=DOK:(2~{S})-2-(4-chlorophenyl)-3-methyl-1-spiro[1,3-benzodioxole-2,4-piperidine]-1-yl-butan-1-one'>DOK</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.36&#8491;</td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=DOK:(2~{S})-2-(4-chlorophenyl)-3-methyl-1-spiro[1,3-benzodioxole-2,4-piperidine]-1-yl-butan-1-one'>DOK</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RHO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6fk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fk6 OCA], [https://pdbe.org/6fk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fk6 RCSB], [https://www.ebi.ac.uk/pdbsum/6fk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fk6 ProSAT]</span></td></tr>
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<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=6fk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fk6 OCA], [http://pdbe.org/6fk6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fk6 RCSB], [http://www.ebi.ac.uk/pdbsum/6fk6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fk6 ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/OPSD_BOVIN OPSD_BOVIN]] Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth. Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change leading to G-protein activation and release of all-trans retinal (By similarity).<ref>PMID:16908857</ref> <ref>PMID:17060607</ref>
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[https://www.uniprot.org/uniprot/OPSD_BOVIN OPSD_BOVIN] Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth. Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change leading to G-protein activation and release of all-trans retinal (By similarity).<ref>PMID:16908857</ref> <ref>PMID:17060607</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In the degenerative eye disease retinitis pigmentosa (RP), protein misfolding leads to fatal consequences for cell metabolism and rod and cone cell survival. To stop disease progression, a therapeutic approach focuses on stabilizing inherited protein mutants of the G protein-coupled receptor (GPCR) rhodopsin using pharmacological chaperones (PC) that improve receptor folding and trafficking. In this study, we discovered stabilizing nonretinal small molecules by virtual and thermofluor screening and determined the crystal structure of pharmacologically stabilized opsin at 2.4 A resolution using one of the stabilizing hits (S-RS1). Chemical modification of S-RS1 and further structural analysis revealed the core binding motif of this class of rhodopsin stabilizers bound at the orthosteric binding site. Furthermore, previously unobserved conformational changes are visible at the intradiscal side of the seven-transmembrane helix bundle. A hallmark of this conformation is an open channel connecting the ligand binding site with the membrane and the intradiscal lumen of rod outer segments. Sufficient in size, the passage permits the exchange of hydrophobic ligands such as retinal. The results broaden our understanding of rhodopsin's conformational flexibility and enable therapeutic drug intervention against rhodopsin-related retinitis pigmentosa.
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Ligand channel in pharmacologically stabilized rhodopsin.,Mattle D, Kuhn B, Aebi J, Bedoucha M, Kekilli D, Grozinger N, Alker A, Rudolph MG, Schmid G, Schertler GFX, Hennig M, Standfuss J, Dawson RJP Proc Natl Acad Sci U S A. 2018 Mar 19. pii: 1718084115. doi:, 10.1073/pnas.1718084115. PMID:29555765<ref>PMID:29555765</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6fk6" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bovin]]
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[[Category: Bos taurus]]
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[[Category: Dawson, R]]
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[[Category: Large Structures]]
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[[Category: Mattle, D]]
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[[Category: Dawson R]]
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[[Category: Standfuss, J]]
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[[Category: Mattle D]]
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[[Category: G protein-coupled receptor]]
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[[Category: Standfuss J]]
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[[Category: Kintegral membrane protein]]
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[[Category: Membrane]]
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[[Category: Membrane protein]]
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[[Category: Photoreceptor protein]]
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[[Category: Receptor]]
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[[Category: Retinitis pigmentosa]]
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[[Category: Rhodopsin]]
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[[Category: Sensory transduction]]
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[[Category: Signaling protein]]
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[[Category: Small molecule complex]]
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[[Category: Transducer photoreceptor]]
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[[Category: Vision]]
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Current revision

Crystal structure of N2C/D282C stabilized opsin bound to RS01

PDB ID 6fk6

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