8fd1: Difference between revisions
New page: '''Unreleased structure''' The entry 8fd1 is ON HOLD Authors: Salom, D., Palczewski, K., Kiser, P.D. Description: Crystal structure of photoactivated rhodopsin in complex with a nanobo... |
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==Crystal structure of photoactivated rhodopsin in complex with a nanobody== | |||
<StructureSection load='8fd1' size='340' side='right'caption='[[8fd1]], [[Resolution|resolution]] 4.25Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8fd1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FD1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.25Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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'>[https://proteopedia.org/fgij/fg.htm?mol=8fd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fd1 OCA], [https://pdbe.org/8fd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fd1 RCSB], [https://www.ebi.ac.uk/pdbsum/8fd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fd1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Rhodopsin is a prototypical G protein-coupled receptor (GPCR) critical for vertebrate vision. Research on GPCR signaling states has been facilitated using llama-derived nanobodies (Nbs), some of which bind to the intracellular surface to allosterically modulate the receptor. Extracellularly binding allosteric nanobodies have also been investigated, but the structural basis for their activity has not been resolved to date. Here, we report a library of Nbs that bind to the extracellular surface of rhodopsin and allosterically modulate the thermodynamics of its activation process. Crystal structures of Nb2 in complex with native rhodopsin reveal a mechanism of allosteric modulation involving extracellular loop 2 and native glycans. Nb2 binding suppresses Schiff base deprotonation and hydrolysis and prevents intracellular outward movement of helices five and six - a universal activation event for GPCRs. Nb2 also mitigates protein misfolding in a disease-associated mutant rhodopsin. Our data show the power of nanobodies to modulate the photoactivation of rhodopsin and potentially serve as therapeutic agents for disease-associated rhodopsin misfolding. | |||
Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain.,Wu A, Salom D, Hong JD, Tworak A, Watanabe K, Pardon E, Steyaert J, Kandori H, Katayama K, Kiser PD, Palczewski K Nat Commun. 2023 Aug 25;14(1):5209. doi: 10.1038/s41467-023-40911-9. PMID:37626045<ref>PMID:37626045</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8fd1" style="background-color:#fffaf0;"></div> | ||
[[Category: Kiser | |||
[[Category: Palczewski | ==See Also== | ||
*[[Rhodopsin 3D structures|Rhodopsin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Kiser PD]] | |||
[[Category: Palczewski K]] | |||
[[Category: Salom D]] | |||
Latest revision as of 15:08, 23 October 2024
Crystal structure of photoactivated rhodopsin in complex with a nanobodyCrystal structure of photoactivated rhodopsin in complex with a nanobody
Structural highlights
FunctionOPSD_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).[1] [2] Publication Abstract from PubMedRhodopsin is a prototypical G protein-coupled receptor (GPCR) critical for vertebrate vision. Research on GPCR signaling states has been facilitated using llama-derived nanobodies (Nbs), some of which bind to the intracellular surface to allosterically modulate the receptor. Extracellularly binding allosteric nanobodies have also been investigated, but the structural basis for their activity has not been resolved to date. Here, we report a library of Nbs that bind to the extracellular surface of rhodopsin and allosterically modulate the thermodynamics of its activation process. Crystal structures of Nb2 in complex with native rhodopsin reveal a mechanism of allosteric modulation involving extracellular loop 2 and native glycans. Nb2 binding suppresses Schiff base deprotonation and hydrolysis and prevents intracellular outward movement of helices five and six - a universal activation event for GPCRs. Nb2 also mitigates protein misfolding in a disease-associated mutant rhodopsin. Our data show the power of nanobodies to modulate the photoactivation of rhodopsin and potentially serve as therapeutic agents for disease-associated rhodopsin misfolding. Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain.,Wu A, Salom D, Hong JD, Tworak A, Watanabe K, Pardon E, Steyaert J, Kandori H, Katayama K, Kiser PD, Palczewski K Nat Commun. 2023 Aug 25;14(1):5209. doi: 10.1038/s41467-023-40911-9. PMID:37626045[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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