- PDB-7k5i: SARS-COV-2 nsp1 in complex with human 40S ribosome -
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Basic information
Entry
Database: PDB / ID: 7k5i
Title
SARS-COV-2 nsp1 in complex with human 40S ribosome
Components
(40S ribosomal protein ...) x 32
40S ribosomal rRNA18S
60S ribosomal protein L41
Host translation inhibitor nsp1
Receptor of activated protein C kinase 1
Keywords
RIBOSOME/VIRAL PROTEIN / nsp1 / 40S / RIBOSOME-VIRAL PROTEIN complex
Function / homology
Function and homology information
negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of peptidyl-serine phosphorylation / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity ...negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of peptidyl-serine phosphorylation / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / mammalian oogenesis stage / supercoiled DNA binding / activation-induced cell death of T cells / neural crest cell differentiation / NF-kappaB complex / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of phagocytosis / erythrocyte homeostasis / rRNA modification in the nucleus and cytosol / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / pigmentation / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / negative regulation of translational frameshifting / Protein hydroxylation / BH3 domain binding / TOR signaling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / T cell proliferation involved in immune response / Peptide chain elongation / iron-sulfur cluster binding / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response / phagocytic cup / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / erythrocyte development / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Protein methylation / spindle assembly / Nuclear events stimulated by ALK signaling in cancer / ribosomal small subunit export from nucleus / positive regulation of intrinsic apoptotic signaling pathway / rough endoplasmic reticulum / laminin binding / translation regulator activity / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / positive regulation of cell cycle / translation initiation factor binding / signaling adaptor activity / gastrulation / Maturation of protein E / Maturation of protein E / MDM2/MDM4 family protein binding / positive regulation of microtubule polymerization / cytosolic ribosome / ER Quality Control Compartment (ERQC) / Mitotic Prometaphase / DNA-(apurinic or apyrimidinic site) endonuclease activity Similarity search - Function
K homology (KH) domain / 40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ubiquitin-like protein FUBI / GMP Synthetase; Chain A, domain 3 / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 ...K homology (KH) domain / 40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ubiquitin-like protein FUBI / GMP Synthetase; Chain A, domain 3 / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / S27a-like superfamily / 40S Ribosomal protein S10 / : / Ribosomal protein S7e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein S27a / Ribosomal protein S17e, conserved site / Ribosomal protein S27a / Ribosomal protein S17e signature. / Ribosomal protein S27a / Ribosomal protein S3Ae, conserved site / Ribosomal protein S3Ae signature. / Ribosomal protein S30 / Ribosomal protein S30 / Ribosomal protein S2, eukaryotic/archaeal / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / Ribosomal protein S27e signature. / 40S ribosomal protein S4, C-terminal domain / 40S ribosomal protein S4 C-terminus / Ribosomal protein S4e, N-terminal, conserved site / Ribosomal protein S4e signature. / Ribosomal protein S3, eukaryotic/archaeal / Ribosomal protein S19e / Ribosomal protein S8e, conserved site / Ribosomal protein S19e / Ribosomal protein S8e signature. / Ribosomal_S19e / Ribosomal protein S6, eukaryotic / Ribosomal protein S7e / Ribosomal protein S7e / 40S ribosomal protein S1/3, eukaryotes / Ribosomal protein S19A/S15e / Ribosomal protein S17e / Ribosomal protein S17e-like superfamily / Ribosomal S17 / 40S ribosomal protein S11, N-terminal / Ribosomal_S17 N-terminal / : / Ribosomal S24e conserved site / Ribosomal protein S24e signature. / Ribosomal protein S4e, N-terminal / RS4NT (NUC023) domain / Ribosomal protein S4, KOW domain / Ribosomal protein S4e / Ribosomal protein S4e, central region / Ribosomal protein S4e, central domain superfamily / Ribosomal family S4e / Ribosomal protein S23, eukaryotic/archaeal / Ribosomal protein S6/S6e/A/B/2, conserved site / Ribosomal protein S6e signature. / Ribosomal protein S24e / Ribosomal protein S24e / Ribosomal protein S27 / Ribosomal protein S27, zinc-binding domain superfamily / Ribosomal protein S27 / Ribosomal protein S17, archaeal/eukaryotic / Ribosomal protein S8e / Ribosomal protein S3Ae / Ribosomal S3Ae family / Ribosomal S3Ae family / Ribosomal protein S28e conserved site / Ribosomal protein S28e signature. / Ribosomal protein S28e / Ribosomal protein S28e / Ribosomal protein S6e / Ribosomal protein S6e / Ribosomal protein S5/S7, eukaryotic/archaeal / Ribosomal protein S6e / Ribosomal protein S13/S15, N-terminal Similarity search - Domain/homology
: / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Replicase polyprotein 1ab / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS3 ...: / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Replicase polyprotein 1ab / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS12 / Small ribosomal subunit protein eS19 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS10 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein eS1 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS9 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS17 / Small ribosomal subunit protein eS4, X isoform / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein uS19 / Small ribosomal subunit protein eS24 / Small ribosomal subunit protein eS25 / Small ribosomal subunit protein eS26 / Small ribosomal subunit protein eS28 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Small ribosomal subunit protein eS32 / Ubiquitin-ribosomal protein eS31 fusion protein / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein RACK1 / Ubiquitin-ribosomal protein eS31 fusion protein Similarity search - Component
Biological species
Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human)
Method
ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å
Journal: bioRxiv / Year: 2020 Title: SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism. Authors: Ming Shi / Longfei Wang / Pietro Fontana / Setu Vora / Ying Zhang / Tian-Min Fu / Judy Lieberman / Hao Wu / Abstract: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly contagious virus that underlies the current COVID-19 pandemic. SARS-CoV-2 is thought to disable various features of host ...The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly contagious virus that underlies the current COVID-19 pandemic. SARS-CoV-2 is thought to disable various features of host immunity and cellular defense. The SARS-CoV-2 nonstructural protein 1 (Nsp1) is known to inhibit host protein translation and could be a target for antiviral therapy against COVID-19. However, how SARS-CoV-2 circumvents this translational blockage for the production of its own proteins is an open question. Here, we report a bipartite mechanism of SARS-CoV-2 Nsp1 which operates by: (1) hijacking the host ribosome via direct interaction of its C-terminal domain (CT) with the 40S ribosomal subunit and (2) specifically lifting this inhibition for SARS-CoV-2 via a direct interaction of its N-terminal domain (NT) with the 5' untranslated region (5' UTR) of SARS-CoV-2 mRNA. We show that while Nsp1-CT is sufficient for binding to 40S and inhibition of host protein translation, the 5' UTR of SARS-CoV-2 mRNA removes this inhibition by binding to Nsp1-NT, suggesting that the Nsp1-NT-UTR interaction is incompatible with the Nsp1-CT-40S interaction. Indeed, lengthening the linker between Nsp1-NT and Nsp1-CT of Nsp1 progressively reduced the ability of SARS-CoV-2 5' UTR to escape the translational inhibition, supporting that the incompatibility is likely steric in nature. The short SL1 region of the 5' UTR is required for viral mRNA translation in the presence of Nsp1. Thus, our data provide a comprehensive view on how Nsp1 switches infected cells from host mRNA translation to SARS-CoV-2 mRNA translation, and that Nsp1 and 5' UTR may be targeted for anti-COVID-19 therapeutics.
#112 - Apr 2009 Oct and Sox Transcription Factors similarity (1)
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Assembly
Deposited unit
R: 40S ribosomal protein S17 2: 40S ribosomal rRNA18S d: 40S ribosomal protein S29 D: 40S ribosomal protein S3 F: 40S ribosomal protein S5 K: 40S ribosomal protein S10 M: 40S ribosomal protein S12 P: 40S ribosomal protein S15 Q: 40S ribosomal protein S16 S: 40S ribosomal protein S18 T: 40S ribosomal protein S19 U: 40S ribosomal protein S20 Z: 40S ribosomal protein S25 c: 40S ribosomal protein S28 f: 40S ribosomal protein S27a g: Receptor of activated protein C kinase 1 A: 40S ribosomal protein SA B: 40S ribosomal protein S3a C: 40S ribosomal protein S2 E: 40S ribosomal protein S4, X isoform G: 40S ribosomal protein S6 H: 40S ribosomal protein S7 I: 40S ribosomal protein S8 J: 40S ribosomal protein S9 L: 40S ribosomal protein S11 N: 40S ribosomal protein S13 O: 40S ribosomal protein S14 V: 40S ribosomal protein S21 W: 40S ribosomal protein S15a X: 40S ribosomal protein S23 Y: 40S ribosomal protein S24 a: 40S ribosomal protein S26 b: 40S ribosomal protein S27 e: 40S ribosomal protein S30 h: 60S ribosomal protein L41 1: Host translation inhibitor nsp1 hetero molecules
40S ribosomal protein ... , 32 types, 32 molecules RdDFKMPQSTUZcfABCEGHIJLNOVWXYabe
#1: Protein
40SribosomalproteinS17 / Small ribosomal subunit protein eS17
Mass: 15578.156 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P08708
#3: Protein
40SribosomalproteinS29 / Small ribosomal subunit protein uS14
Mass: 6690.821 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62273
#4: Protein
40SribosomalproteinS3 / Small ribosomal subunit protein uS3
Mass: 26729.369 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P23396, DNA-(apurinic or apyrimidinic site) lyase
#5: Protein
40SribosomalproteinS5 / Small ribosomal subunit protein uS7
Mass: 22913.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46782
#6: Protein
40SribosomalproteinS10 / Small ribosomal subunit protein eS10
Mass: 18933.846 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46783
#7: Protein
40SribosomalproteinS12 / Small ribosomal subunit protein eS12
Mass: 14538.987 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P25398
#8: Protein
40SribosomalproteinS15 / RIG protein / Small ribosomal subunit protein uS19
Mass: 17076.207 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62841
#9: Protein
40SribosomalproteinS16 / Small ribosomal subunit protein uS9
Mass: 16477.377 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62249
#10: Protein
40SribosomalproteinS18 / Ke-3 / Ke3 / Small ribosomal subunit protein uS13
Mass: 17759.777 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62269
#11: Protein
40SribosomalproteinS19 / Small ribosomal subunit protein eS19
Mass: 16091.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P39019
#12: Protein
40SribosomalproteinS20 / Small ribosomal subunit protein uS10
Mass: 13398.763 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P60866
#13: Protein
40SribosomalproteinS25 / Small ribosomal subunit protein eS25
Mass: 13776.224 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62851
#14: Protein
40SribosomalproteinS28 / Small ribosomal subunit protein eS28
Mass: 7855.052 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62857
#15: Protein
40SribosomalproteinS27a / Ubiquitin carboxyl extension protein 80 / Ubiquitin-40S ribosomal protein S27a
Mass: 17083.053 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q5RKT7, UniProt: P62979*PLUS
Mass: 32883.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P08865
#18: Protein
40SribosomalproteinS3a / Small ribosomal subunit protein eS1 / v-fos transformation effector protein / Fte-1
Mass: 30002.061 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P61247
#19: Protein
40SribosomalproteinS2 / 40S ribosomal protein S4 / Protein LLRep3 / Small ribosomal subunit protein uS5
Mass: 31376.516 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P15880
#20: Protein
40SribosomalproteinS4, Xisoform / SCR10 / Single copy abundant mRNA protein / Small ribosomal subunit protein eS4
Mass: 29654.869 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62701
#21: Protein
40SribosomalproteinS6 / Phosphoprotein NP33 / Small ribosomal subunit protein eS6
Mass: 28751.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62753
#22: Protein
40SribosomalproteinS7 / Small ribosomal subunit protein eS7
Mass: 22168.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62081
#23: Protein
40SribosomalproteinS8 / Small ribosomal subunit protein eS8
Mass: 24263.387 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62241
#24: Protein
40SribosomalproteinS9 / Small ribosomal subunit protein uS4
Mass: 22641.564 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46781
#25: Protein
40SribosomalproteinS11 / Small ribosomal subunit protein uS17
Mass: 18468.826 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62280
#26: Protein
40SribosomalproteinS13 / Small ribosomal subunit protein uS15
Mass: 17259.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62277
#27: Protein
40SribosomalproteinS14 / Small ribosomal subunit protein uS11
Mass: 16302.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62263
#28: Protein
40SribosomalproteinS21 / Small ribosomal subunit protein eS21
Mass: 9124.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63220
#29: Protein
40SribosomalproteinS15a / Small ribosomal subunit protein uS8
Mass: 14865.555 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62244
#30: Protein
40SribosomalproteinS23 / Small ribosomal subunit protein uS12
Mass: 15844.666 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62266
#31: Protein
40SribosomalproteinS24 / Small ribosomal subunit protein eS24
Mass: 15463.333 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62847
#32: Protein
40SribosomalproteinS26 / Small ribosomal subunit protein eS26
Mass: 11776.989 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62854
#33: Protein
40SribosomalproteinS27 / Metallopan-stimulin 1 / MPS-1 / Small ribosomal subunit protein eS27
Mass: 9480.186 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P42677
#34: Protein
40SribosomalproteinS30 / Small ribosomal subunit protein eS30
Mass: 6668.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62861
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Protein , 2 types, 2 molecules g1
#16: Protein
ReceptorofactivatedproteinCkinase1 / Cell proliferation-inducing gene 21 protein / Guanine nucleotide-binding protein subunit beta-2- ...Cell proliferation-inducing gene 21 protein / Guanine nucleotide-binding protein subunit beta-2-like 1 / Guanine nucleotide-binding protein subunit beta-like protein 12.3 / Human lung cancer oncogene 7 protein / HLC-7 / Receptor for activated C kinase / Small ribosomal subunit protein RACK1
Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244
#36: Protein
Hosttranslationinhibitornsp1 / Leader protein / Non-structural protein 1 / nsp1
Mass: 19801.287 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Production host: Escherichia coli BL21 (bacteria) / References: UniProt: P0DTD1
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