The impact of viral RNA on the association free energies of capsid protein assembly: bacteriophage MS2 as a case study
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- 作者：Karim M. ElSawy
- 关键词：Association free energy ; Self ; assembly ; Viruses ; Virus assembly ; MS2 virus
- 刊名：Journal of Molecular Modeling
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：23
- 期：2
- 全文大小：
- 刊物类别：Chemistry and Materials Science
- 刊物主题：Computer Applications in Chemistry; Molecular Medicine; Computer Appl. in Life Sciences; Characterization and Evaluation of Materials; Theoretical and Computational Chemistry;
- 出版者：Springer Berlin Heidelberg
- ISSN：0948-5023
- 卷排序：23
文摘
A large number of single-stranded RNA viruses assemble their capsid and their genomic material simultaneously. The RNA viral genome plays multiple roles in this process that are currently only partly understood. In this work, we investigated the thermodynamic basis of the role of viral RNA on the assembly of capsid proteins. The viral capsid of bacteriophage MS2 was considered as a case study. The MS2 virus capsid is composed of 60 AB and 30 CC protein dimers. We investigated the effect of RNA stem loop (the translational repressor TR) binding to the capsid dimers on the dimer–dimer relative association free energies. We found that TR binding results in destabilization of AB self-association compared with AB and CC association. This indicates that the association of the AB and CC dimers is the most likely assembly pathway for the MS2 virus, which explains the experimental observation of alternating patterns of AB and CC dimers in dominant assembly intermediates of the MS2 virus. The presence of viral RNA, therefore, dramatically channels virus assembly to a limited number of pathways, thereby enhancing the efficiency of virus self-assembly process. Interestingly, Thr59Ser and Thr45Ala mutations of the dimers, in the absence of RNA stem loops, lead to stabilization of AB self-association compared with the AB and CC associations, thereby channelling virus assembly towards a fivefold (AB)5 pentamer intermediate, providing a testable hypothesis of our thermodynamic arguments.