7kkj: Difference between revisions

Revision as of 15:26, 18 October 2023

Structure of anti-SARS-CoV-2 Spike nanobody mNb6

Structural highlights

7kkj is a 2 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:	CL, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike. Science. 2020 Nov 5. pii: science.abe3255. doi: 10.1126/science.abe3255. PMID:33154106 doi:https://dx.doi.org/10.1126/science.abe3255

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike. Science. 2020 Nov 5. pii: science.abe3255. doi: 10.1126/science.abe3255. PMID:33154106 doi:https://dx.doi.org/10.1126/science.abe3255

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='7kkj' size='340' side='right'caption='[[7kkj]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7kkj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. 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 [http://proteopedia.org/fgij/fg.htm?mol=7KKJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7kkj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. 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='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>
+</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7kkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kkj OCA], [http://pdbe.org/7kkj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kkj RCSB], [http://www.ebi.ac.uk/pdbsum/7kkj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kkj ProSAT]</span></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;">
@@ Line 16: / Line 17: @@
 </div>
 <div class="pdbe-citations 7kkj" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
 == References ==
 <references/>
@@ Line 21: / Line 25: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Synthetic construct sequences]]
+[[Category: Synthetic construct]]
-[[Category: Anand, A A]]
+[[Category: Anand AA]]
-[[Category: Azumaya, C M]]
+[[Category: Azumaya CM]]
-[[Category: Barile-Hill, A W]]
+[[Category: Barile-Hill AW]]
-[[Category: Barsi-Rhyne, B]]
+[[Category: Barsi-Rhyne B]]
-[[Category: Belyy, V]]
+[[Category: Belyy V]]
-[[Category: Billesboelle, C B]]
+[[Category: Billesboelle CB]]
-[[Category: Boone, M]]
+[[Category: Boone M]]
-[[Category: Brilot, A F]]
+[[Category: Brilot AF]]
-[[Category: Bulkley, D]]
+[[Category: Bulkley D]]
-[[Category: Chio, C M]]
+[[Category: Chio CM]]
-[[Category: Chio, U S]]
+[[Category: Chio US]]
-[[Category: Consortium, QCRG Structural Biology]]
+[[Category: Desphande I]]
-[[Category: Desphande, I]]
+[[Category: Dickinson S]]
-[[Category: Dickinson, S]]
+[[Category: Diwanji D]]
-[[Category: Diwanji, D]]
+[[Category: Dobzinski N]]
-[[Category: Dobzinski, N]]
+[[Category: Faust BF]]
-[[Category: Faust, B F]]
+[[Category: Garcia-Sastre A]]
-[[Category: Garcia-Sastre, A]]
+[[Category: Gupta M]]
-[[Category: Gupta, M]]
+[[Category: Gupta S]]
-[[Category: Gupta, S]]
+[[Category: Hoppe N]]
-[[Category: Hoppe, N]]
+[[Category: Jin M]]
-[[Category: Jin, M]]
+[[Category: Kratochvil HT]]
-[[Category: Kratochvil, H T]]
+[[Category: Krogan NJ]]
-[[Category: Krogan, N J]]
+[[Category: Leon K]]
-[[Category: Leon, K]]
+[[Category: Li F]]
-[[Category: Li, F]]
+[[Category: Liang J]]
-[[Category: Liang, J]]
+[[Category: Liu Y]]
-[[Category: Liu, Y]]
+[[Category: Manglik A]]
-[[Category: Manglik, A]]
+[[Category: Merz GE]]
-[[Category: Merz, G E]]
+[[Category: Moss F]]
-[[Category: Moss, F]]
+[[Category: Nguyen HC]]
-[[Category: Nguyen, H C]]
+[[Category: Nock S]]
-[[Category: Nock, S]]
+[[Category: Ott M]]
-[[Category: Ott, M]]
+[[Category: Pospiech T]]
-[[Category: Pospiech, T]]
+[[Category: Pourmal S]]
-[[Category: Pourmal, S]]
+[[Category: Puchades C]]
-[[Category: Puchades, C]]
+[[Category: QCRG Structural Biology Consortium]]
-[[Category: Ralston, C Y]]
+[[Category: Ralston CY]]
-[[Category: Rezelj, V]]
+[[Category: Rezelj V]]
-[[Category: Rizo, A N]]
+[[Category: Rizo AN]]
-[[Category: Sangwan, S]]
+[[Category: Sangwan S]]
-[[Category: Saunders, R A]]
+[[Category: Saunders RA]]
-[[Category: Schaefer, K]]
+[[Category: Schaefer K]]
-[[Category: Schoof, M S]]
+[[Category: Schoof MS]]
-[[Category: Simoneau, C R]]
+[[Category: Simoneau CR]]
-[[Category: Smith, A M]]
+[[Category: Smith AM]]
-[[Category: Sun, M]]
+[[Category: Sun M]]
-[[Category: Swaney, D L]]
+[[Category: Swaney DL]]
-[[Category: Thompson, M C]]
+[[Category: Thompson MC]]
-[[Category: Trenker, R]]
+[[Category: Trenker R]]
-[[Category: Vignuzzi, M]]
+[[Category: Vignuzzi M]]
-[[Category: Walter, P]]
+[[Category: Walter P]]
-[[Category: White, K M]]
+[[Category: White KM]]
-[[Category: Zha, B S]]
+[[Category: Zha BS]]
-[[Category: Zhang, K]]
+[[Category: Zhang K]]
-[[Category: Zimanyi, M]]
+[[Category: Zimanyi M]]
-[[Category: Complex]]
-[[Category: Immune system]]
-[[Category: Nanobody]]
-[[Category: Vhh]]

7kkj: Difference between revisions

Revision as of 15:26, 18 October 2023

Structure of anti-SARS-CoV-2 Spike nanobody mNb6

Structural highlights

Publication Abstract from PubMed

See Also

References

Contents

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