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题 目Viral glycoproteins mediated membrane fusion studied in situ by Cryo-electron tomography

报告人: Dr. Sai LiSenior Research Associate

Oxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust for Human Genetics, University of Oxford

时 间201794(周一)13:00-14:00

地 点北京大学老化学楼东配楼101报告厅

主持人宋晨 研究员

摘 要:

Enveloped viruses consist of large variety of families. Notorious members of enveloped viruses, such as HIV, hepatitis B&C virus and Influenza virus are responsible for millions of deaths each year. The genome of an enveloped virus is wrapped by a lipid bilayer, which is inturn coated with viral glycoproteins (GP). In general, these GP spikes reside on viral surfaces in oligomeric complexes. They mediate viral recognition of the host, binding, entry and membrane fusion and are therefore targets of the immune system. Understanding the infection mechanism requires solving the GP structures in situ on different stages of viral entry. However, this is complicated by the pleomorphicity of enveloped viruses and the flexibility of the GP. Here we combined cryo-electron tomography and subtomogram averaging (STA) to shed light on the fusion strategy of viruses with class-I and class-II fusion proteins. These studies not only provided the highest resolution structure of GP solved using STA, but also captured the first intermediate and target membrane-inserted structure of a fusion protein between the pre- and postfusion state. Furthermore, we have also discovered the first class-IV viral fusion protein with the help of Volta-phase plate. All together, these studies enriched our knowledge of how GP helped enveloped viruses adopting different strategies for entry and unpacking.


李赛,2006 年毕业于武汉大学应用物理系后,他先后于德国斯图加特大学和哥廷根大学获得了物理学硕士和生物物理学博士。2013 年起,他加入牛津大学粒子成像中心Juha Huiskonen 研究组从事研究工作。在那里,他主要的研究兴趣集中在开发冷冻电镜断层成像及重构技术,并应用这些技术对带包膜的新发性传染病病毒进行高分辨率原位重构。他希望通过解析包膜病毒以及包膜病毒与宿主复合体的原位结构,对病毒的生命周期以及病毒—宿主的相互作用提供新的阐释。