Forum 01/13/2005

“Reovirus at 10, 9, 8, 7 Resolution and Beyond: So Whats the Big Deal?”

Timothy Baker – Dept. of Chemistry & Biochemistry University of California, San Diego

Viruses have evolved several ways to accomplish the common goal of delivering their genetic payload to host cells.  Enveloped viruses typically employ specialized glycoproteins to facilitate fusion of viral and host membranes, which culminates in release of the viral genome to the cytoplasm of infected cells.  Extensive studies of Class I and II fusion proteins have provided important clues about how viruses solve this important challenge.  Though many non-enveloped viruses must also penetrate a host membrane barrier, very little is known about the mechanisms involved.  We have been using electron cryo-microscopy (cryoEM) and three-dimensional (3D) image reconstruction methods to study members of the Reoviridae family of viruses and have recently achieved better than 7 resolution in our study of the mammalian orthoreovirus.  The 3D reconstruction of the virion, coupled with results from X-ray studies of crystals of reovirus cores and of the heterohexamer of two viral outer capsid proteins, provides new insights about how the different structural proteins facilitate viral infection.  Notably, portions of the reovirus & 1 protein that do not appear in the (&1 & crystal structure are visible in our cryoEM reconstruction.  The N-terminus is one such portion and is believed to be responsible for initial events involving the delivery of reovirus cores to the host cell cytoplasm.  The seminar will focus (pun intended) on the power of cryoEM as a tool to obtain structural insights about macromolecular function.

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