7N0D

Cryo-EM structure of the tetrameric form of SARS-CoV-2 nsp10-nsp14 (E191A)-RNA complex


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.50 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme.

Liu, C.Shi, W.Becker, S.T.Schatz, D.G.Liu, B.Yang, Y.

(2021) Science 373: 1142-1146

  • DOI: https://doi.org/10.1126/science.abi9310
  • Primary Citation of Related Structures:  
    7N0B, 7N0C, 7N0D

  • PubMed Abstract: 

    Coronavirus 3′-to-5′ exoribonuclease (ExoN), residing in the nonstructural protein (nsp) 10–nsp14 complex, boosts replication fidelity by proofreading RNA synthesis and is critical for the virus life cycle. ExoN also recognizes and excises nucleotide analog inhibitors incorporated into the nascent RNA, undermining the effectiveness of nucleotide analog–based antivirals. Here we present cryo–electron microscopy structures of both wild-type and mutant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nsp10-nsp14 in complex with an RNA substrate bearing a 3′-end mismatch at resolutions ranging from 2.5 to 3.9 angstroms. The structures reveal the molecular determinants of ExoN substrate specificity and offer insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. Our findings provide guidance for rational design of improved anticoronavirus therapies.


  • Organizational Affiliation

    Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Non-structural protein 10A,
C,
H [auth E],
J [auth G]
139Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
Gene Names: rep1a-1b
UniProt
Find proteins for P0DTD1 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTD1 
Go to UniProtKB:  P0DTD1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DTD1
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Proofreading exoribonucleaseB,
D,
I [auth F],
K [auth H]
527Severe acute respiratory syndrome coronavirus 2Mutation(s): 1 
Gene Names: rep1a-1b
EC: 3.1.13
UniProt
Find proteins for P0DTD1 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTD1 
Go to UniProtKB:  P0DTD1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DTD1
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains LengthOrganismImage
RNA (5'-R(*GP*GP*GP*GP*AP*UP*GP*UP*GP*AP*UP*UP*UP*UP*AP*AP*UP*AP*G)-3')E [auth T],
L [auth I]
27Severe acute respiratory syndrome coronavirus 2
Sequence Annotations
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Entity ID: 4
MoleculeChains LengthOrganismImage
RNA (5'-R(*CP*UP*AP*UP*UP*AP*AP*AP*AP*UP*CP*AP*CP*C)-3')F [auth K],
M [auth L]
22Severe acute respiratory syndrome coronavirus 2
Sequence Annotations
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  • Reference Sequence

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Entity ID: 5
MoleculeChains LengthOrganismImage
RNA (5'-R(*CP*CP*CP*CP*C)-3')G [auth P],
N [auth J]
5Severe acute respiratory syndrome coronavirus 2
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1N7
Query on 1N7

Download Ideal Coordinates CCD File 
BA [auth D],
LA [auth H]
CHAPSO
C32 H59 N2 O8 S
GUQQBLRVXOUDTN-XOHPMCGNSA-O
ZN
Query on ZN

Download Ideal Coordinates CCD File 
AA [auth D]
CA [auth E]
DA [auth E]
GA [auth F]
HA [auth F]
AA [auth D],
CA [auth E],
DA [auth E],
GA [auth F],
HA [auth F],
IA [auth F],
JA [auth G],
KA [auth G],
NA [auth H],
O [auth A],
OA [auth H],
P [auth A],
PA [auth H],
S [auth B],
T [auth B],
U [auth B],
V [auth C],
W [auth C],
Y [auth D],
Z [auth D]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
EA [auth F]
FA [auth F]
MA [auth H]
Q [auth B]
R [auth B]
EA [auth F],
FA [auth F],
MA [auth H],
Q [auth B],
R [auth B],
X [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.50 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2021-07-28
    Type: Initial release
  • Version 1.1: 2021-08-04
    Changes: Database references
  • Version 1.2: 2021-08-25
    Changes: Database references
  • Version 1.3: 2021-09-22
    Changes: Database references
  • Version 1.4: 2024-05-29
    Changes: Data collection