| Autor: |
Hill, Chris H., Pekarek, Lukas, Napthine, Sawsan, Kibe, Anuja, Firth, Andrew E., Graham, Stephen C., Caliskan, Neva, Brierley, Ian |
| Předmět: |
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| Zdroj: |
Nature Communications; 12/9/2021, Vol. 12 Issue 1, p1-16, 16p |
| Abstrakt: |
Programmed –1 ribosomal frameshifting (PRF) in cardioviruses is activated by the 2A protein, a multi-functional virulence factor that also inhibits cap-dependent translational initiation. Here we present the X-ray crystal structure of 2A and show that it selectively binds to a pseudoknot-like conformation of the PRF stimulatory RNA element in the viral genome. Using optical tweezers, we demonstrate that 2A stabilises this RNA element, likely explaining the increase in PRF efficiency in the presence of 2A. Next, we demonstrate a strong interaction between 2A and the small ribosomal subunit and present a cryo-EM structure of 2A bound to initiated 70S ribosomes. Multiple copies of 2A bind to the 16S rRNA where they may compete for binding with initiation and elongation factors. Together, these results define the structural basis for RNA recognition by 2A, show how 2A-mediated stabilisation of an RNA pseudoknot promotes PRF, and reveal how 2A accumulation may shut down translation during virus infection. Many RNA viruses employ programmed –1 ribosomal frameshifting (PRF) to expand their coding capacity and optimize production of viral proteins. Here, the authors report structural and biophysical analysis of protein 2A from a cardiovirus, with insights into the mechanism of its PRF-stimulatory function. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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