+Open data
-Basic information
Entry | Database: PDB / ID: 7ddp | ||||||
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Title | Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD | ||||||
Components |
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Keywords | HYDROLASE/VIRAL PROTEIN / pangolin / RBD / ACE2 / PROTEIN BINDING / HYDROLASE-VIRAL PROTEIN complex | ||||||
Function / homology | Function and homology information positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / regulation of vasoconstriction / regulation of cardiac conduction ...positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / tryptophan transport / positive regulation of gap junction assembly / regulation of systemic arterial blood pressure by renin-angiotensin / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / : / angiotensin maturation / maternal process involved in female pregnancy / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / Attachment and Entry / carboxypeptidase activity / negative regulation of signaling receptor activity / regulation of cytokine production / positive regulation of cardiac muscle contraction / viral life cycle / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / regulation of transmembrane transporter activity / brush border membrane / endocytosis involved in viral entry into host cell / cilium / negative regulation of ERK1 and ERK2 cascade / endocytic vesicle membrane / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / virus receptor activity / regulation of cell population proliferation / regulation of inflammatory response / endopeptidase activity / Induction of Cell-Cell Fusion / Potential therapeutics for SARS / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / receptor-mediated virion attachment to host cell / membrane => GO:0016020 / symbiont entry into host cell / membrane raft / apical plasma membrane / fusion of virus membrane with host plasma membrane / endoplasmic reticulum lumen / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / cell surface / extracellular space / extracellular exosome / zinc ion binding / extracellular region / membrane / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Pangolin coronavirus | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / Resolution: 3.4 Å | ||||||
Authors | Niu, S. / Wang, J. / Wang, H.W. / Qi, J.X. / Wang, Q.H. / Gao, G.F. | ||||||
Citation | Journal: EMBO J / Year: 2021 Title: Molecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin. Authors: Sheng Niu / Jia Wang / Bin Bai / Lili Wu / Anqi Zheng / Qian Chen / Pei Du / Pengcheng Han / Yanfang Zhang / Yunfei Jia / Chengpeng Qiao / Jianxun Qi / Wen-Xia Tian / Hong-Wei Wang / Qihui ...Authors: Sheng Niu / Jia Wang / Bin Bai / Lili Wu / Anqi Zheng / Qian Chen / Pei Du / Pengcheng Han / Yanfang Zhang / Yunfei Jia / Chengpeng Qiao / Jianxun Qi / Wen-Xia Tian / Hong-Wei Wang / Qihui Wang / George Fu Gao / Abstract: Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated ...Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated from pangolins, GX/P2V/2017 and GD/1/2019, to human angiotensin-converting enzyme 2 (hACE2), the receptor of SARS-CoV-2. We find that the spike protein receptor-binding domain (RBD) of pangolin CoVs binds to hACE2 as efficiently as the SARS-CoV-2 RBD in vitro. Furthermore, incorporation of pangolin CoV RBDs allows entry of pseudotyped VSV particles into hACE2-expressing cells. A screen for binding of pangolin CoV RBDs to ACE2 orthologs from various species suggests a broader host range than that of SARS-CoV-2. Additionally, cryo-EM structures of GX/P2V/2017 and GD/1/2019 RBDs in complex with hACE2 show their molecular binding in modes similar to SARS-CoV-2 RBD. Introducing the Q498H substitution found in pangolin CoVs into the SARS-CoV-2 RBD expands its binding capacity to ACE2 homologs of mouse, rat, and European hedgehog. These findings suggest that these two pangolin CoVs may infect humans, highlighting the necessity of further surveillance of pangolin CoVs. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7ddp.cif.gz | 150.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ddp.ent.gz | 121.3 KB | Display | PDB format |
PDBx/mmJSON format | 7ddp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dd/7ddp ftp://data.pdbj.org/pub/pdb/validation_reports/dd/7ddp | HTTPS FTP |
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-Related structure data
Related structure data | 30653MC 7ddoC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 69153.664 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2, UNQ868/PRO1885 / Production host: unidentified baculovirus References: UniProt: Q9BYF1, angiotensin-converting enzyme 2, Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases | ||
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#2: Protein | Mass: 23408.482 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Pangolin coronavirus / Production host: unidentified baculovirus / References: UniProt: A0A6G6A1M4 | ||
#3: Chemical | ChemComp-ZN / | ||
#4: Sugar | ChemComp-NAG / 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 | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: NO |
-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 FIELDBright-field microscopy |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 135699 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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