View source for 7kkj


==Structure of anti-SARS-CoV-2 Spike nanobody mNb6==
<StructureSection load='7kkj' size='340' side='right'caption='[[7kkj]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KKJ 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7kkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kkj OCA], [https://pdbe.org/7kkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kkj RCSB], [https://www.ebi.ac.uk/pdbsum/7kkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kkj ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The SARS-CoV-2 virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryogenic electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.

An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.,Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, Boone M, Billesbolle CB, Puchades C, Azumaya CM, Kratochvil HT, Zimanyi M, Deshpande I, Liang J, Dickinson S, Nguyen HC, Chio CM, Merz GE, Thompson MC, Diwanji D, Schaefer K, Anand AA, Dobzinski N, Zha BS, Simoneau CR, Leon K, White KM, Chio US, Gupta M, Jin M, Li F, Liu Y, Zhang K, Bulkley D, Sun M, Smith AM, Rizo AN, Moss F, Brilot AF, Pourmal S, Trenker R, Pospiech T, Gupta S, Barsi-Rhyne B, Belyy V, Barile-Hill AW, Nock S, Liu Y, Krogan NJ, Ralston CY, Swaney DL, Garcia-Sastre A, Ott M, Vignuzzi M, Walter P, Manglik A Science. 2020 Nov 5. pii: science.abe3255. doi: 10.1126/science.abe3255. PMID:33154106<ref>PMID:33154106</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kkj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Anand AA]]
[[Category: Azumaya CM]]
[[Category: Barile-Hill AW]]
[[Category: Barsi-Rhyne B]]
[[Category: Belyy V]]
[[Category: Billesboelle CB]]
[[Category: Boone M]]
[[Category: Brilot AF]]
[[Category: Bulkley D]]
[[Category: Chio CM]]
[[Category: Chio US]]
[[Category: Desphande I]]
[[Category: Dickinson S]]
[[Category: Diwanji D]]
[[Category: Dobzinski N]]
[[Category: Faust BF]]
[[Category: Garcia-Sastre A]]
[[Category: Gupta M]]
[[Category: Gupta S]]
[[Category: Hoppe N]]
[[Category: Jin M]]
[[Category: Kratochvil HT]]
[[Category: Krogan NJ]]
[[Category: Leon K]]
[[Category: Li F]]
[[Category: Liang J]]
[[Category: Liu Y]]
[[Category: Manglik A]]
[[Category: Merz GE]]
[[Category: Moss F]]
[[Category: Nguyen HC]]
[[Category: Nock S]]
[[Category: Ott M]]
[[Category: Pospiech T]]
[[Category: Pourmal S]]
[[Category: Puchades C]]
[[Category: QCRG Structural Biology Consortium]]
[[Category: Ralston CY]]
[[Category: Rezelj V]]
[[Category: Rizo AN]]
[[Category: Sangwan S]]
[[Category: Saunders RA]]
[[Category: Schaefer K]]
[[Category: Schoof MS]]
[[Category: Simoneau CR]]
[[Category: Smith AM]]
[[Category: Sun M]]
[[Category: Swaney DL]]
[[Category: Thompson MC]]
[[Category: Trenker R]]
[[Category: Vignuzzi M]]
[[Category: Walter P]]
[[Category: White KM]]
[[Category: Zha BS]]
[[Category: Zhang K]]
[[Category: Zimanyi M]]