7f5g

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Current revision (17:09, 29 November 2023) (edit) (undo)
 
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==The crystal structure of RBD-Nanobody complex, DL4 (SA4)==
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<StructureSection load='7f5g' size='340' side='right'caption='[[7f5g]]' scene=''>
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<StructureSection load='7f5g' size='340' side='right'caption='[[7f5g]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7f5g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F5G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F5G FirstGlance]. <br>
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</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=7f5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f5g OCA], [https://pdbe.org/7f5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f5g RCSB], [https://www.ebi.ac.uk/pdbsum/7f5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f5g ProSAT]</span></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]] 1.75&#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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7f5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f5g OCA], [https://pdbe.org/7f5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f5g RCSB], [https://www.ebi.ac.uk/pdbsum/7f5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f5g ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</ref> mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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SARS-CoV-2 engages with human cells through the binding of its Spike receptor-binding domain (S-RBD) to the receptor ACE2. Molecular blocking of this engagement represents a proven strategy to treat COVID-19. Here, we report a single-chain antibody (nanobody, DL4) isolated from immunized alpaca with picomolar affinity to RBD. DL4 neutralizes SARS-CoV-2 pseudoviruses with an IC(50) of 0.101 mug mL(-1) (6.2 nM). A crystal structure of the DL4-RBD complex at 1.75-A resolution unveils the interaction detail and reveals a direct competition mechanism for DL4's ACE2-blocking and hence neutralizing activity. The structural information allows us to rationally design a mutant with higher potency. Our work adds diversity of neutralizing nanobodies against SARS-CoV-2 and should encourage protein engineering to improve antibody affinities in general.
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Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2.,Li T, Zhou B, Li Y, Huang S, Luo Z, Zhou Y, Lai Y, Gautam A, Bourgeau S, Wang S, Bao J, Tan J, Lavillette D, Li D Int J Biol Macromol. 2022 Jun 1;209(Pt A):1379-1388. doi: , 10.1016/j.ijbiomac.2022.04.096. Epub 2022 Apr 20. PMID:35460753<ref>PMID:35460753</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 7f5g" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Antibody 3D structures|Antibody 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Severe acute respiratory syndrome coronavirus 2]]
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[[Category: Vicugna pacos]]
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[[Category: Lai Y]]
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[[Category: Li D]]
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[[Category: Li T]]
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[[Category: Tan J]]
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[[Category: Zhou Y]]

Current revision

The crystal structure of RBD-Nanobody complex, DL4 (SA4)

PDB ID 7f5g

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