6MZI

CryoEM structure of human enterovirus D68 expanded 1 particle (pH 6.5, 4 degrees Celsius, 3 min)

Summary for 6MZI

• Entry DOI: 10.2210/pdb6mzi/pdb
• EMDB information: 9055
• Descriptor: viral protein 1, viral protein 3, viral protein 2, ... (4 entities in total)
• Functional Keywords: virus, genome release, acid
• Biological source: Enterovirus D68; More
• Total number of polymer chains: 4
• Total formula weight: 94937.22

Authors

Liu, Y.,Rossmann, M.G. (deposition date: 2018-11-05, release date: 2018-12-19, Last modification date: 2024-03-13)

Primary citation

Liu, Y.,Sheng, J.,van Vliet, A.L.W.,Buda, G.,van Kuppeveld, F.J.M.,Rossmann, M.G.
Molecular basis for the acid-initiated uncoating of human enterovirus D68.
Proc. Natl. Acad. Sci. U.S.A., 115:E12209-E12217, 2018

PubMed Abstract: 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.

PubMed: 30530701
DOI: 10.1073/pnas.1803347115

Experimental method

ELECTRON MICROSCOPY (3.46 Å)