6BFU

Glycan shield and fusion activation of a deltacoronavirus spike glycoprotein fine-tuned for enteric infections


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.50 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Glycan Shield and Fusion Activation of a Deltacoronavirus Spike Glycoprotein Fine-Tuned for Enteric Infections.

Xiong, X.Tortorici, M.A.Snijder, J.Yoshioka, C.Walls, A.C.Li, W.McGuire, A.T.Rey, F.A.Bosch, B.J.Veesler, D.

(2018) J Virol 92

  • DOI: https://doi.org/10.1128/JVI.01628-17
  • Primary Citation of Related Structures:  
    6BFU

  • PubMed Abstract: 

    Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome. They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection. The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response. We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus. Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts. The structure further reveals a shortened S 2 ' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant. This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity. IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes. We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide. Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus. PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.


  • Organizational Affiliation

    Department of Biochemistry, University of Washington, Seattle, Washington, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Spike protein
A, B, C
1,024Porcine deltacoronavirusMutation(s): 0 
UniProt
Find proteins for A0A140ESF1 (Porcine deltacoronavirus)
Explore A0A140ESF1 
Go to UniProtKB:  A0A140ESF1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A140ESF1
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
BA [auth b],
D,
DA [auth d],
F,
FA [auth f],
BA [auth b],
D,
DA [auth d],
F,
FA [auth f],
O,
OA [auth o],
Q,
S
6N-Glycosylation
Glycosylation Resources
GlyTouCan:  G56014GC
GlyCosmos:  G56014GC
GlyGen:  G56014GC
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
CA [auth c],
G,
GA [auth g],
P,
PA [auth p],
CA [auth c],
G,
GA [auth g],
P,
PA [auth p],
T
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseI,
IA [auth i],
V
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
AB [auth B]
BB [auth B]
CB [auth B]
DB [auth B]
EB [auth B]
AB [auth B],
BB [auth B],
CB [auth B],
DB [auth B],
EB [auth B],
FB [auth B],
GB [auth C],
HB [auth C],
IB [auth C],
JB [auth C],
KB [auth C],
LB [auth C],
MB [auth C],
NB [auth C],
QA [auth A],
RA [auth A],
SA [auth A],
TA [auth A],
UA [auth A],
VA [auth A],
WA [auth A],
XA [auth A],
YA [auth B],
ZA [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.50 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States1R01GM120553

Revision History  (Full details and data files)

  • Version 1.0: 2017-11-22
    Type: Initial release
  • Version 1.1: 2017-12-06
    Changes: Author supporting evidence
  • Version 1.2: 2018-01-24
    Changes: Structure summary
  • Version 1.3: 2019-02-06
    Changes: Data collection, Other, Structure summary
  • Version 1.4: 2019-04-03
    Changes: Data collection, Database references
  • Version 1.5: 2020-01-01
    Changes: Author supporting evidence
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary