8r40

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Current revision (08:05, 6 November 2024) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8r40 is ON HOLD until Paper Publication
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==Crystal structure of diabody CR57 in complex with rabies virus protein G domain III==
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<StructureSection load='8r40' size='340' side='right'caption='[[8r40]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8r40]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rabies_virus_CVS-11 Rabies virus CVS-11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8R40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R40 FirstGlance]. <br>
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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]] 2.7&#8491;</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=GOL:GLYCEROL'>GOL</scene></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=8r40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r40 OCA], [https://pdbe.org/8r40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r40 RCSB], [https://www.ebi.ac.uk/pdbsum/8r40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r40 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GLYCO_RABVC GLYCO_RABVC] Attaches the virus to host cellular receptor, inducing endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and cell membrane. There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind glycoprotein and thereby facilitate rabies virus entry into cells (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Host-cell entry of the highly pathogenic rabies virus (RABV) is mediated by glycoprotein (G) spikes, which also comprise the primary target for the humoral immune response. RABV glycoprotein (RABV-G) displays several antigenic sites that are targeted by neutralizing monoclonal antibodies (mAbs). In this study, we determined the epitope of a potently neutralizing human mAb, CR57, which we engineered into a diabody format to facilitate crystallization. We report the crystal structure of the CR57 diabody alone at 2.38 A resolution, and in complex with RABV-G domain III at 2.70 A resolution. The CR57-RABV-G structure reveals critical interactions at the antigen interface, which target the conserved "KLCGVL" peptide and residues proximal to it on RABV-G. Structural analysis combined with a cell-cell fusion assay demonstrates that CR57 effectively inhibits RABV-G-mediated fusion by obstructing the fusogenic transitions of the spike protein. Altogether, this investigation provides a structural perspective on RABV inhibition by a potently neutralizing human antibody.
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Authors: Kedari, A., Rissanen, I.
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Structural insight into rabies virus neutralization revealed by an engineered antibody scaffold.,Kedari A, Iheozor-Ejiofor R, Salminen P, Ugurlu H, Makela AR, Levanov L, Vapalahti O, Hytonen VP, Saksela K, Rissanen I Structure. 2024 Oct 25:S0969-2126(24)00437-4. doi: 10.1016/j.str.2024.10.002. PMID:39471803<ref>PMID:39471803</ref>
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Description: Crystal structure of diabody CR57 in complex with rabies virus protein G domain III
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Rissanen, I]]
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<div class="pdbe-citations 8r40" style="background-color:#fffaf0;"></div>
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[[Category: Kedari, A]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Rabies virus CVS-11]]
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[[Category: Kedari A]]
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[[Category: Rissanen I]]

Current revision

Crystal structure of diabody CR57 in complex with rabies virus protein G domain III

PDB ID 8r40

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