期刊
ANNUAL REVIEW OF BIOPHYSICS, VOL 48
卷 48, 期 -, 页码 495-514出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-biophys-052118-115611
关键词
virus assembly; RNA packaging signals; genome organization; mathematical modeling; single-molecule FCS; normal mode analysis; Gillespie algorithms; Hamiltonian paths
类别
资金
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
- Medical Research Council [MR/N021517/1] Funding Source: Medline
- Wellcome Trust [110146, 110145, 110145/Z/15/Z] Funding Source: Medline
- BBSRC [BB/L021803/1] Funding Source: UKRI
- EPSRC [EP/R023204/1] Funding Source: UKRI
- Wellcome Trust [110145/Z/15/Z] Funding Source: Wellcome Trust
Viruses, entities composed of nucleic acids, proteins, and in some cases lipids lack the ability to replicate outside their target cells. Their components self-assemble at the nanoscale with exquisite precision-a key to their biological success in infection. Recent advances in structure determination and the development of biophysical tools such as single-molecule spectroscopy and noncovalent mass spectrometry allow unprecedented access to the detailed assembly mechanisms of simple virions. Coupling these techniques with mathematical modeling and bioinformatics has uncovered a previously unsuspected role for genomic RNA in regulating formation of viral capsids, revealing multiple, dispersed RNA sequence/structure motifs [packaging signals (PSs)] that bind cognate coat proteins cooperatively. The PS ensemble controls assembly efficiency and accounts for the packaging specificity seen in vivo. The precise modes of action of the PSs vary between viral families, but this common principle applies across many viral families, including major human pathogens. These insights open up the opportunity to block or repurpose PS function in assembly for both novel antiviral therapy and gene/drug/vaccine applications.
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