Why are G-quadruplexes good at preventing protein aggregation?

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.