Part I: Virus Structures
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Harrison begins his talk by asking why most non-enveloped viruses and some enveloped viruses are symmetrical in shape. He proceeds to show us lovely images of the structures obtained by x-ray crystallography of numerous viral coat proteins. Deciphering these structures allowed scientists to understand that viral coat proteins form multimers, such as dimers and pentamers, which in turn interact with a scaffold that ensures that the coat proteins are correctly placed. This arrangement results in symmetrically shaped viruses.
In Part 1, Harrison also explains that enveloped viruses infect cells by inducing the fusion of the viral and host cell membranes. He delves deeper into the molecular mechanism of membrane fusion driven by the hemagglutinin or HA protein of the influenza virus in Part 2 of his talk. Non-enveloped viruses, on the other hand, must enter cells by a mechanism other than membrane fusion. This is the focus of Part 3. Using rotavirus as a model, Harrison and his colleagues have used a combination of Xray crystallography and electron cryomicroscopy to decipher how the spike protein on the viral surface changes its conformation and perforates the cell membrane allowing the virus to enter the cell.
Stephen Harrison received his A.B. and Ph.D. from Harvard University. He became interested in molecular structures and began his studies using X-ray crystallography as a graduate student. After receiving his Ph.D., he remained at Harvard and continued his work to improve the resolution of the tomato bushy stunt virus structure. In 1977, after 7 years of study, Harrison obtained the first high-resolution structure of any virus particle. Currently, Harrison is a professor at Harvard Medical School and Children’s Hospital, Boston. He is also an Investigator of the Howard Hughes Medical Institute. His lab studies the atomic structure of macromolecular complexes including viruses and the molecules with which they interact. Harrison is a member of the National Academy of Sciences amongst other honors.
- Ari Helenius iBioSeminar: Cell biology of Virus Entry
- David Baltimore iBioSeminar: Introduction to Viruses and HIV
- Stephen Harrison Short Clip: Viruses Structural Properties
Harrison SC. Viral membrane fusion. Nat Struct Mol Biol. 2008 Jul;15(7):690-8.
Harrison SC. Looking inside adenovirus. Science. 2010 Aug 27;329(5995):1026-7. A Comment on the two papers below..
Liu H, Jin L, Koh SB, Atanasov I, Schein S, Wu L, Zhou ZH. Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks. Science. 2010 Aug 27;329(5995):1038-43..
Reddy VS, Natchiar SK, Stewart PL, Nemerow GR. Crystal structure of human adenovirus at 3.5 A resolution. Science. 2010 Aug 27;329(5995):1071-5..
Settembre EC, Chen JZ, Dormitzer PR, Grigorieff N, Harrison SC. Atomic model of an infectious rotavirus particle. EMBO J. 2011 Jan 19;30(2):408-16.