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bioRxiv · 10.1101/2022.08.23.504968

Why are G-quadruplexes good at preventing protein aggregation?

Litberg, T. J.·Sannapureddi, R. K. R.·Huang, Z.·Son, A.·Sathyamoorthy, B.·Horowitz, S.
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Abstract

Maintaining a healthy protein folding environment is essential for cellular function. Recently, we found that nucleic acids, and G-quadruplexes in particular, are potent chaperones for preventing protein aggregation. With the aid of structure-function and NMR analyses of two G-quadruplex forming sequences, PARP-I and LTR-III, we uncovered several contributing factors that affect G-quadruplexes in preventing protein aggregation. Notably, three factors emerged as vital in determining holdase activity of G-quadruplexes: their structural topology, structural dynamics, and oligomerization state. These factors together appear to largely dictate whether a G-quadruplex is able to prevent partially misfolded proteins from aggregating. Understanding the genesis of G-quadruplexes power as chaperones is an important facet to elucidating various protein aggregation diseases. Key Points- How nucleic acids act as protein chaperones is currently unknown. - G-quadruplexes are excellent at preventing protein aggregation, and here we describe basic tenets of this activity. - This activity could help design treatments for multiple neurodegenerative diseases.

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Litberg, T. J., Sannapureddi, R. K. R., Huang, Z., Son, A., Sathyamoorthy, B., Horowitz, S.. 2022-08-23. Why are G-quadruplexes good at preventing protein aggregation?. https://doi.org/10.1101/2022.08.23.504968

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