[English] 日本語
Yorodumi
- EMDB-45772: Local refinement of BA.5 spike/Nanosota-9 complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-45772
TitleLocal refinement of BA.5 spike/Nanosota-9 complex
Map dataunsharpened local map of BA.5 spike/Nanosota-9 complex
Sample
  • Complex: BA.5 spike/Nanosota-9 complex
    • Complex: BA.5 spike
      • Protein or peptide: Spike glycoprotein
    • Complex: Nanosota-9
      • Protein or peptide: Nanosota-9
Keywordsspike / nanobody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / membrane fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / receptor ligand activity / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane
Similarity search - Function
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2
Similarity search - Domain/homology
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Vicugna pacos (alpaca)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.32 Å
AuthorsYe G / Bu F / Liu B / Li F
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI089728 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI110700 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI171954 United States
CitationJournal: PLoS Pathog / Year: 2024
Title: Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate.
Authors: Gang Ye / Fan Bu / Divyasha Saxena / Hailey Turner-Hubbard / Morgan Herbst / Benjamin Spiller / Brian E Wadzinski / Lanying Du / Bin Liu / Jian Zheng / Fang Li /
Abstract: Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic ...Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic viruses due to their favorable properties. In this study, we identified a novel nanobody, Nanosota-9, which demonstrates high potency against a wide range of Omicron subvariants both in vitro and in a mouse model. Cryo-EM data revealed that Nanosota-9 neutralizes Omicron through a unique mechanism: two Nanosota-9 molecules crosslink two receptor-binding domains (RBDs) of the trimeric Omicron spike protein, preventing the RBDs from binding to the ACE2 receptor. This mechanism explains its strong anti-Omicron potency. Additionally, the Nanosota-9 binding epitopes on the spike protein are relatively conserved among Omicron subvariants, contributing to its broad anti-Omicron spectrum. Combined with our recently developed structure-guided in vitro evolution approach for nanobodies, Nanosota-9 has the potential to serve as the foundation for a superior anti-Omicron therapeutic.
History
DepositionJul 16, 2024-
Header (metadata) releaseNov 20, 2024-
Map releaseNov 20, 2024-
UpdateDec 11, 2024-
Current statusDec 11, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_45772.png

Downloads & links

-
Map

FileDownload / File: emd_45772.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationunsharpened local map of BA.5 spike/Nanosota-9 complex
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.89 Å/pix.
x 384 pix.
= 339.968 Å		0.89 Å/pix.
x 384 pix.
= 339.968 Å		0.89 Å/pix.
x 384 pix.
= 339.968 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.88533 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0949
Minimum - Maximum-0.5268356 - 1.193765
Average (Standard dev.)0.00018275288 (±0.0074494514)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 339.96786 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: sharpened local map of BA.5 spike/Nanosota-9 complex

Fileemd_45772_additional_1.map
Annotationsharpened local map of BA.5 spike/Nanosota-9 complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: local half map A of BA.5 spike/Nanosota-9 complex

Fileemd_45772_half_map_1.map
Annotationlocal half map_A of BA.5 spike/Nanosota-9 complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: local half map B of BA.5 spike/Nanosota-9 complex

Fileemd_45772_half_map_2.map
Annotationlocal half map_B of BA.5 spike/Nanosota-9 complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : BA.5 spike/Nanosota-9 complex

EntireName: BA.5 spike/Nanosota-9 complex
Components
  • Complex: BA.5 spike/Nanosota-9 complex
    • Complex: BA.5 spike
      • Protein or peptide: Spike glycoprotein
    • Complex: Nanosota-9
      • Protein or peptide: Nanosota-9

-
Supramolecule #1: BA.5 spike/Nanosota-9 complex

SupramoleculeName: BA.5 spike/Nanosota-9 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

-
Supramolecule #2: BA.5 spike

SupramoleculeName: BA.5 spike / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 / Details: Recombinant BA.5 spike protein
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

-
Supramolecule #3: Nanosota-9

SupramoleculeName: Nanosota-9 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2
Source (natural)Organism: Vicugna pacos (alpaca)

-
Macromolecule #1: Spike glycoprotein

MacromoleculeName: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Details: BA.5 spike / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weightTheoretical: 136.6345 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QCVNLITRTQ SYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH AISGTNGTKR FDNPVLPFND GVYFASTEKS NIIRGWIFG TTLDSKTQSL LIVNNATNVV IKVCEFQFCN DPFLDVYYHK NNKSWMESEF RVYSSANNCT FEYVSQPFLM D LEGKQGNF ...String:
QCVNLITRTQ SYTNSFTRGV YYPDKVFRSS VLHSTQDLFL PFFSNVTWFH AISGTNGTKR FDNPVLPFND GVYFASTEKS NIIRGWIFG TTLDSKTQSL LIVNNATNVV IKVCEFQFCN DPFLDVYYHK NNKSWMESEF RVYSSANNCT FEYVSQPFLM D LEGKQGNF KNLREFVFKN IDGYFKIYSK HTPINLGRDL PQGFSALEPL VDLPIGINIT RFQTLLALHR SYLTPGDSSS GW TAGAAAY YVGYLQPRTF LLKYNENGTI TDAVDCALDP LSETKCTLKS FTVEKGIYQT SNFRVQPTES IVRFPNITNL CPF DEVFNA TRFASVYAWN RKRISNCVAD YSVLYNFAPF FAFKCYGVSP TKLNDLCFTN VYADSFVIRG NEVSQIAPGQ TGNI ADYNY KLPDDFTGCV IAWNSNKLDS KVGGNYNYRY RLFRKSNLKP FERDISTEIY QAGNKPCNGV AGVNCYFPLQ SYGFR PTYG VGHQPYRVVV LSFELLHAPA TVCGPKKSTN LVKNKCVNFN FNGLTGTGVL TESNKKFLPF QQFGRDIADT TDAVRD PQT LEILDITPCS FGGVSVITPG TNTSNQVAVL YQGVNCTEVP VAIHADQLTP TWRVYSTGSN VFQTRAGCLI GAEYVNN SY ECDIPIGAGI CASYQTQTKS HAGARSVASQ SIIAYTMSLG AENSVAYSNN SIAIPTNFTI SVTTEILPVS MTKTSVDC T MYICGDSTEC SNLLLQYGSF CTQLKRALTG IAVEQDKNTQ EVFAQVKQIY KTPPIKYFGG FNFSQILPDP SKPSKRSPI EDLLFNKVTL ADAGFIKQYG DCLGDIAARD LICAQKFNGL TVLPPLLTDE MIAQYTSALL AGTITSGWTF GAGPALQIPF PMQMAYRFN GIGVTQNVLY ENQKLIANQF NSAIGKIQDS LSSTPSALGK LQDVVNHNAQ ALNTLVKQLS SKFGAISSVL N DILSRLDP PEAEVQIDRL ITGRLQSLQT YVTQQLIRAA EIRASANLAA TKMSECVLGQ SKRVDFCGKG YHLMSFPQSA PH GVVFLHV TYVPAQEKNF TTAPAICHDG KAHFPREGVF VSNGTHWFVT QRNFYEPQII TTDNTFVSGN CDVVIGIVNN TVY DPLQPE LDSFKEELDK YFKNHTSPDV DLGDISGINA SVVNIQKEID RLNEVAKNLN ESLIDLQELG KYEQYIKGSG YIPE APRDG QAYVRKDGEW VLLSTFLGHH HHHH

UniProtKB: Spike glycoprotein

-
Macromolecule #2: Nanosota-9

MacromoleculeName: Nanosota-9 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Vicugna pacos (alpaca)
Molecular weightTheoretical: 16.311601 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
QVQLQESGGG LVQPGGSLRL SCTASGIALH THATGWFRQA PGKEREGVSC ISSGDGTTYY EDSVEGRFTI SRDNAKNTVY LQMNSLKLE DTAVYYCAAD PGAVCHSGSY YYTDDDFYYR GQGTQVTVSS GGQHHHHHHG AYPYDVPDYA S

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 54.8 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.1 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 431183
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

8ios


Chain - Source name: PDB / Chain - Initial model type: experimental model
Output model

PDB-9co7:
Local refinement of BA.5 spike/Nanosota-9 complex

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more