PDBsum entry 6crs

Virus

PDB id: 6crs

Contents

Protein chains

212 a.a.

244 a.a.

235 a.a.

References listed in PDB file

Key reference

• Title: Molecular basis for the acid-Initiated uncoating of human enterovirus d68.
• Authors: Y.Liu, J.Sheng, A.L.W.Van vliet, G.Buda, F.J.M.Van kuppeveld, M.G.Rossmann.
• Ref.: Proc Natl Acad Sci U S A, 2018, 115, E12209. [DOI no: 10.1073/pnas.1803347115]
• PubMed id: 30530701

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.