Cryo-EM structures reveal two distinct conformational states in a picornavirus cell entry intermediate

Citation:

Pranav N. M. Shah, David J. Filman, Krishanthi S. Karunatilaka, Emma L. Hesketh, Elisabetta Groppelli, Mike Strauss, and James M. Hogle. 2020. “Cryo-EM structures reveal two distinct conformational states in a picornavirus cell entry intermediate.” PLOS Pathogens, 16, 9, Pp. 1-26. Publisher's Version

Abstract:

Author summary Nonenveloped viruses need to provide mechanisms that allow their genomes to be delivered across membranes. This process remains poorly understood. For enteroviruses such as poliovirus, genome delivery involves a program of conformational changes that include expansion of the particle and externalization of two normally internal peptides, VP4 and the VP1 N-terminus, which then insert into the cell membrane, triggering endocytosis and the creation of pores that facilitate the transfer of the viral RNA genome across the endosomal membrane. This manuscript describes five high-resolution cryo-EM structures of altered poliovirus particles that represent a number of intermediates along this pathway. The structures reveal several surprising findings, including the discovery of a new intermediate that is expanded, but has not yet externalized the membrane interactive peptides; the clear identification of a unique exit site for the VP1 N-terminus; the demonstration that the externalized VP1 N-terminus partitions between two different sites in a temperature-dependent fashion; direct visualization of an amphipathic helix at the N-terminus of VP1 in an ideal position for interaction with cellular membranes; and the observation that a significant portion of VP4 remains inside the particle and accounts for a density feature that had previously been ascribed to part of the viral RNA. These findings represent significant additions to our understanding of the cell entry process of an important class of human pathogens.
Last updated on 10/02/2020