Self-Assembly of Measles Virus Nucleocapsid-like Particles: Kinetics and RNA Sequence Dependence
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- 作者：Dr. Sigrid Milles ; Dr. Malene Ringkjø ; bing Jensen ; Dr. Guillaume Communie ; Damien Maurin ; Dr. Guy Schoehn ; Prof. Rob W. H. Ruigrok and Dr. Martin Blackledge
- 刊名：Angewandte Chemie International Edition
- 出版年：2016
- 出版时间：August 1, 2016
- 年：2016
- 卷：55
- 期：32
- 页码：9356-9360
- 全文大小：2143K
- ISSN：1521-3773
文摘
Measles virus RNA genomes are packaged into helical nucleocapsids (NCs), comprising thousands of nucleo-proteins (N) that bind the entire genome. N-RNA provides the template for replication and transcription by the viral polymerase and is a promising target for viral inhibition. Elucidation of mechanisms regulating this process has been severely hampered by the inability to controllably assemble NCs. Here, we demonstrate self-organization of N into NC-like particles in vitro upon addition of RNA, providing a simple and versatile tool for investigating assembly. Real-time NMR and fluorescence spectroscopy reveals biphasic assembly kinetics. Remarkably, assembly depends strongly on the RNA-sequence, with the genomic 5′ end and poly-Adenine sequences assembling efficiently, while sequences such as poly-Uracil are incompetent for NC formation. This observation has important consequences for understanding the assembly process.