Norovirus Capsid Proteins Self-Assemble through Biphasic Kinetics via Long-Lived Stave-like Intermediates

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• 作者：Guillaume Tresset ; Cl茅mence Le Coeur ; Jean-Fran莽ois Bryche ; Mouna Tatou ; Mehdi Zeghal ; Annie Charpilienne ; Didier Poncet ; Doru Constantin ; St茅phane Bressanelli
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：October 16, 2013
• 年：2013
• 卷：135
• 期：41
• 页码：15373-15381
• 全文大小：457K
• 年卷期：v.135,no.41(October 16, 2013)
• ISSN：1520-5126

文摘

The self-assembly kinetics for a norovirus capsid protein were probed by time-resolved small-angle X-ray scattering and then analyzed by singular value decomposition and global fitting. Only three species contribute to the total scattering intensities: dimers, intermediates comprising some 11 dimers, and icosahedral T = 3 capsids made up of 90 dimers. Three-dimensional reconstructions of the intermediate robustly show a stave-like shape consistent with an arrangement of two pentameric units connected by an interstitial dimer. Upon triggering of self-assembly, the biphasic kinetics consist of a fast step in which dimers are assembled into intermediates, followed by a slow step in which intermediates interlock into capsids. This simple kinetic model reproduces experimental data with an excellent agreement over 6 decades in time and with nanometer resolution. The extracted form factors are robust against changes in experimental conditions. These findings challenge and complement currently accepted models for the assembly of norovirus capsids.