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Structure paper

TitleMolecular basis for the acid-initiated uncoating of human enterovirus D68.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 115, Issue 52, Page E12209-E12217, Year 2018
Publish dateDec 26, 2018
AuthorsYue Liu / Ju Sheng / Arno L W van Vliet / Geeta Buda / Frank J M van Kuppeveld / Michael G Rossmann /
PubMed AbstractEnterovirus D68 (EV-D68) belongs to a group of enteroviruses that contain a single positive-sense RNA genome surrounded by an icosahedral capsid. Like common cold viruses, EV-D68 mainly causes ...Enterovirus D68 (EV-D68) belongs to a group of enteroviruses that contain a single positive-sense RNA genome surrounded by an icosahedral capsid. Like common cold viruses, EV-D68 mainly causes respiratory infections and is acid-labile. The molecular mechanism by which the acid-sensitive EV-D68 virions uncoat and deliver their genome into a host cell is unknown. Using cryoelectron microscopy (cryo-EM), we have determined the structures of the full native virion and an uncoating intermediate [the A (altered) particle] of EV-D68 at 2.2- and 2.7-Å resolution, respectively. These structures showed that acid treatment of EV-D68 leads to particle expansion, externalization of the viral protein VP1 N termini from the capsid interior, and formation of pores around the icosahedral twofold axes through which the viral RNA can exit. Moreover, because of the low stability of EV-D68, cryo-EM analyses of a mixed population of particles at neutral pH and following acid treatment demonstrated the involvement of multiple structural intermediates during virus uncoating. Among these, a previously undescribed state, the expanded 1 ("E1") particle, shows a majority of internal regions (e.g., the VP1 N termini) to be ordered as in the full native virion. Thus, the E1 particle acts as an intermediate in the transition from full native virions to A particles. Together, the present work delineates the pathway of EV-D68 uncoating and provides the molecular basis for the acid lability of EV-D68 and of the related common cold viruses.
External linksProc Natl Acad Sci U S A / PubMed:30530701 / PubMed Central
MethodsEM (single particle)
Resolution2.17 - 3.75 Å
Structure data

EMDB-7567, PDB-6crp:
CryoEM structure of human enterovirus D68 abortive product 1 (pH 7.2 and 4 degrees Celsius)
Method: EM (single particle) / Resolution: 3.24 Å

EMDB-7569, PDB-6crr:
CryoEM structure of human enterovirus D68 full native virion (pH 7.2 and 4 degrees Celsius)
Method: EM (single particle) / Resolution: 3.24 Å

EMDB-7571, PDB-6crs:
CryoEM structure of human enterovirus D68 A-particle (pH 7.2 and 4 degrees Celsius)
Method: EM (single particle) / Resolution: 3.24 Å

EMDB-7572, PDB-6cru:
CryoEM structure of human enterovirus D68 emptied particle (pH 7.2 and 4 degrees Celsius)
Method: EM (single particle) / Resolution: 3.32 Å

EMDB-7583, PDB-6cs3:
CryoEM structure of human enterovirus D68 expanded 1 particle (pH 7.2 and 4 degrees Celsius)
Method: EM (single particle) / Resolution: 3.31 Å

EMDB-7589, PDB-6cs4:
CryoEM structure of human enterovirus D68 A-particle (pH 5.5 and 33 degrees Celsius)
Method: EM (single particle) / Resolution: 2.73 Å

EMDB-7592, PDB-6cs5:
CryoEM structure of human enterovirus D68 abortive product 2 (pH 7.2 and 4 degrees Celsius)
Method: EM (single particle) / Resolution: 3.24 Å

EMDB-7593, PDB-6cs6:
CryoEM structure of human enterovirus D68 A-particle (pH 5.5 and room temperature)
Method: EM (single particle) / Resolution: 3.25 Å

EMDB-7598, PDB-6csa:
CryoEM structure of human enterovirus D68 emptied particle (pH 5.5 and room temperature)
Method: EM (single particle) / Resolution: 3.75 Å

EMDB-7599, PDB-6csg:
CryoEM structure of human enterovirus D68 full native virion
Method: EM (single particle) / Resolution: 2.17 Å

EMDB-7600, PDB-6csh:
CryoEM structure of human enterovirus D68 emptied particle (pH 5.5 and 33 degrees Celsius)
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-9053:
CryoEM structure of human enterovirus D68 full native virion (pH 6.5, 4 degrees Celsius, 3 min)
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-9054:
CryoEM structure of human enterovirus D68 A-particle (pH 6.5, 4 degrees Celsius, 3 min)
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-9055, PDB-6mzi:
CryoEM structure of human enterovirus D68 expanded 1 particle (pH 6.5, 4 degrees Celsius, 3 min)
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-9056:
CryoEM structure of human enterovirus D68 full native virion (pH 6.5, room temperature, 3 min)
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-9057:
CryoEM structure of human enterovirus D68 A-particle (pH 6.5, room temperature, 3 min)
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-9058:
CryoEM structure of human enterovirus D68 full native virion (pH 6.0, room temperature, 30 sec)
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-9059:
CryoEM structure of human enterovirus D68 A-particle (pH 6.0, room temperature, 30 sec)
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-9060:
CryoEM structure of human enterovirus D68 A-particle (pH 6.0, room temperature, 3 min)
Method: EM (single particle) / Resolution: 3.46 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • enterovirus d68
KeywordsVIRUS / genome release / acid

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