Xing Zhang,1 Lei Jin,1 Qin Fang,2 Wong H. Hui,3 and Z. Hong Zhou1,3 *
1 Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095-7364, USA
2 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
3 California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095-7364, USA
* Correspondence: hong.zhou@ucla.edu
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Abstract
To achieve cell entry, many nonenveloped viruses must transform from a dormant to a primed state. In contrast to the membrane fusion mechanism of enveloped viruses (e.g., influenza virus), this membrane penetration mechanism is poorly understood. Here, using single-particle cryo-electron microscopy, we report a 3.3Å structure of the primed, infectious subvirion particle of aquareovirus. The density map reveals side-chain densities of all types of amino acids (except glycine), enabling construction of a full-atom model of the viral particle. Our structure and biochemical results show that priming involves autocleavage of the membrane penetration protein and suggest that Lys84 and Glu76 may facilitate this autocleavage in a nucleophilic attack. We observe a myristoyl group, covalently linked to the N terminus of the penetration protein and embedded in a hydrophobic pocket. These results suggest a well-orchestrated process of nonenveloped virus entry involving autocleavage of the penetration protein prior to exposure of its membrane-insertion finger. Cell, Volume 141, Issue 3, 472-482, 30 April 2010.
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"The ability to understand the structure of viruses at an atomic level will open avenues for manipulating them for use in drug delivery and propel numerous innovations in treatments of diseases. UCLA is fortunate to have such specialized instrumentation, and the expertise of Professor Zhou and his team to take advantage of these marvelous microscopes."
Dr. Leonard H. Rome, senior associate dean for research of UCLA's David Geffen School of Medicine and associate director of the California NanoSystems Institute. |
"Dr. Zhou's work shows sensational structural results using single particle cryo-electron microscopy to resolve detailed protein structure in a large virus. This was thought to be impossible by many experts not long ago."
Dr. Wah Chiu, professor of biochemistry and molecular biology at Houston-based Baylor College of Medicine. |
"This is a tremendous scientific accomplishment, and we are excited for Dr. Hong Zhou and his team at the CNSI at UCLA. It demonstrates that the FEI Vitrobot™ and Titan Krios™ TEM can be used as a workflow solution to uniquely identify atomic structures within a cell in its native hydrated state and to better understand their function."
Dr. Dominique Hubert, FEI's vice president and general manager for the Life Sciences Division. |