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Yorodumi- PDB-8k4u: Structure of BtKY72 spike receptor-binding domain (RBD) complexed... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8k4u | ||||||
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Title | Structure of BtKY72 spike receptor-binding domain (RBD) complexed with bat ACE2 | ||||||
Components |
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Keywords | VIRAL PROTEIN / BtKY72 RBD ACE2 bat | ||||||
Biological species | Severe acute respiratory syndrome-related coronavirus Rhinolophus landeri (Lander's horseshoe bat) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Su, C. / Qi, J.X. / Gao, G.F. | ||||||
Funding support | 1items
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Citation | Journal: mBio / Year: 2024 Title: Structural characteristics of BtKY72 RBD bound to bat ACE2 reveal multiple key residues affecting ACE2 usage of sarbecoviruses. Authors: Chao Su / Juanhua He / Liang Wang / Yu Hu / Jian Cao / Bin Bai / Jianxun Qi / George Fu Gao / Mengsu Yang / Qihui Wang / Abstract: Two different sarbecoviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, have caused serious challenges to public health. Certain sarbecoviruses utilize angiotensin- ...Two different sarbecoviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, have caused serious challenges to public health. Certain sarbecoviruses utilize angiotensin-converting enzyme 2 (ACE2) as their cellular receptor, whereas some do not, speculatively due to the two deletions in their receptor-binding domain (RBD). However, it remains unclear whether sarbecoviruses with one deletion in the RBD can still bind to ACE2. Here, we showed that two phylogenetically related sarbecoviruses with one deletion, BtKY72 and BM48-31, displayed a different ACE2-usage range. The cryo-electron microscopy structure of BtKY72 RBD bound to bat ACE2 identified a key residue important for the interaction between RBD and ACE2. In addition, we demonstrated that the mutations involving four types of core residues enabled the sarbecoviruses with deletion(s) to bind to human ACE2 (hACE2) and broadened the ACE2 usage of SARS-CoV-2. Our findings help predict the potential hACE2-binding ability to emerge sarbecoviruses and develop pan-sarbecovirus therapeutic agents. IMPORTANCE: Many sarbecoviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), possess the ability to bind to receptor angiotensin-converting enzyme 2 (ACE2) through their ...IMPORTANCE: Many sarbecoviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), possess the ability to bind to receptor angiotensin-converting enzyme 2 (ACE2) through their receptor-binding domain (RBD). However, certain sarbecoviruses with deletion(s) in the RBD lack this capability. In this study, we investigated two closely related short-deletion sarbecoviruses, BtKY72 and BM48-31, and revealed that BtKY72 exhibited a broader ACE2-binding spectrum compared to BM48-31. Structural analysis of the BtKY72 RBD-bat ACE2 complex identifies a critical residue at position 493 contributing to these differences. Furthermore, we demonstrated that the mutations involving four core residues in the RBD enabled the sarbecoviruses with deletion(s) to bind to human ACE2 and expanded the ACE2 usage spectra of SARS-CoV-2. These findings offer crucial insights for accurately predicting the potential threat of newly emerging sarbecoviruses to human health. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8k4u.cif.gz | 151.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8k4u.ent.gz | 116.2 KB | Display | PDB format |
PDBx/mmJSON format | 8k4u.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8k4u_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8k4u_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8k4u_validation.xml.gz | 34.4 KB | Display | |
Data in CIF | 8k4u_validation.cif.gz | 49.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k4/8k4u ftp://data.pdbj.org/pub/pdb/validation_reports/k4/8k4u | HTTPS FTP |
-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 25514.703 Da / Num. of mol.: 1 / Fragment: RBD Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome-related coronavirus Production host: Homo sapiens (human) |
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#2: Protein | Mass: 69443.156 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rhinolophus landeri (Lander's horseshoe bat) Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
#3: Chemical | ChemComp-ZN / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1397414 / Symmetry type: POINT | ||||||||||||||||||||||||
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