+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30653 | |||||||||
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Title | Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD | |||||||||
Map data | Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD | |||||||||
Sample |
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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 / regulation of systemic arterial blood pressure by renin-angiotensin / positive regulation of gap junction assembly / tryptophan transport / 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 / regulation of systemic arterial blood pressure by renin-angiotensin / positive regulation of gap junction assembly / tryptophan transport / regulation of cardiac conduction / regulation of vasoconstriction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / negative regulation of signaling receptor activity / Attachment and Entry / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / membrane => GO:0016020 / negative regulation of smooth muscle cell proliferation / brush border membrane / regulation of transmembrane transporter activity / endocytosis involved in viral entry into host cell / cilium / negative regulation of ERK1 and ERK2 cascade / positive regulation of reactive oxygen species metabolic process / metallopeptidase activity / endocytic vesicle membrane / regulation of cell population proliferation / virus receptor activity / regulation of inflammatory response / endopeptidase activity / Potential therapeutics for SARS / Induction of Cell-Cell Fusion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / receptor-mediated virion attachment to host cell / symbiont entry into host cell / apical plasma membrane / membrane raft / endoplasmic reticulum lumen / fusion of virus membrane with host plasma membrane / 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 / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Pangolin coronavirus | |||||||||
Method | single particle reconstruction / Resolution: 3.4 Å | |||||||||
Authors | Niu S / Wang J / Wang HW / Qi JX / Wang QH / Gao GF | |||||||||
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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_30653.map.gz | 2 MB | EMDB map data format | |
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Header (meta data) | emd-30653-v30.xml emd-30653.xml | 11.6 KB 11.6 KB | Display Display | EMDB header |
Images | emd_30653.png | 204.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30653 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30653 | HTTPS FTP |
-Validation report
Summary document | emd_30653_validation.pdf.gz | 323 KB | Display | EMDB validaton report |
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Full document | emd_30653_full_validation.pdf.gz | 322.5 KB | Display | |
Data in XML | emd_30653_validation.xml.gz | 5.5 KB | Display | |
Data in CIF | emd_30653_validation.cif.gz | 6.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30653 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30653 | HTTPS FTP |
-Related structure data
Related structure data | 7ddpMC 7ddoC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_30653.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.99375 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD
Entire | Name: Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD |
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Components |
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-Supramolecule #1: Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD
Supramolecule | Name: Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: human ACE2
Supramolecule | Name: human ACE2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: unidentified baculovirus |
-Supramolecule #3: GX/P2V/2017 RBD
Supramolecule | Name: GX/P2V/2017 RBD / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Pangolin coronavirus |
Recombinant expression | Organism: unidentified baculovirus |
-Macromolecule #1: Angiotensin-converting enzyme 2
Macromolecule | Name: Angiotensin-converting enzyme 2 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: unidentified baculovirus |
Sequence | String: STIEEQAKTF LDKFNHEAED LFYQSSLASW NYNTNITEEN VQNMNNAGDK WSAFLKEQST LAQMYPLQEI QNLTVKLQLQ ALQQNGSSVL SEDKSKRLNT ILNTMSTIYS TGKVCNPDNP QECLLLEPGL NEIMANSLDY NERLWAWESW RSEVGKQLRP LYEEYVVLKN ...String: STIEEQAKTF LDKFNHEAED LFYQSSLASW NYNTNITEEN VQNMNNAGDK WSAFLKEQST LAQMYPLQEI QNLTVKLQLQ ALQQNGSSVL SEDKSKRLNT ILNTMSTIYS TGKVCNPDNP QECLLLEPGL NEIMANSLDY NERLWAWESW RSEVGKQLRP LYEEYVVLKN EMARANHYED YGDYWRGDYE VNGVDGYDYS RGQLIEDVEH TFEEIKPLYE HLHAYVRAKL MNAYPSYISP IGCLPAHLLG DMWGRFWTNL YSLTVPFGQK PNIDVTDAMV DQAWDAQRIF KEAEKFFVSV GLPNMTQGFW ENSMLTDPGN VQKAVCHPTA WDLGKGDFRI LMCTKVTMDD FLTAHHEMGH IQYDMAYAAQ PFLLRNGANE GFHEAVGEIM SLSAATPKHL KSIGLLSPDF QEDNETEINF LLKQALTIVG TLPFTYMLEK WRWMVFKGEI PKDQWMKKWW EMKREIVGVV EPVPHDETYC DPASLFHVSN DYSFIRYYTR TLYQFQFQEA LCQAAKHEGP LHKCDISNST EAGQKLFNML RLGKSEPWTL ALENVVGAKN MNVRPLLNYF EPLFTWLKDQ NKNSFVGWST DWSPYA |
-Macromolecule #2: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Pangolin coronavirus |
Sequence | String: RVQPTISIVR FPNITNLCPF GEVFNASKFA SVYAWNRKRI SNCVADYSVL YNSTSFSTFK CYGVSPTKLN DLCFTNVYAD SFVVKGDEVR QIAPGQTGVI ADYNYKLPDD FTGCVIAWNS VKQDALTGGN YGYLYRLFRK SKLKPFERDI STEIYQAGST PCNGQVGLNC ...String: RVQPTISIVR FPNITNLCPF GEVFNASKFA SVYAWNRKRI SNCVADYSVL YNSTSFSTFK CYGVSPTKLN DLCFTNVYAD SFVVKGDEVR QIAPGQTGVI ADYNYKLPDD FTGCVIAWNS VKQDALTGGN YGYLYRLFRK SKLKPFERDI STEIYQAGST PCNGQVGLNC YYPLERYGFH PTTGVNYQPF RVVVLSFELL NGPATVCGP |
-Experimental details
-Structure determination
Processing | single particle reconstruction |
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Aggregation state | particle |
-Sample preparation
Concentration | 0.2 mg/mL |
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Buffer | pH: 8 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 135699 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |