Volumetric Interplay between the Conformational States Adopted by DNA Strands from the Promoter Region of the c-MYC Oncogene

Abstract

from the exit tunnel. It has also been shown that positively charged residues can stall translation while still in the exit tunnel, although the mechanism by which stalling occurs is still unknown. Here, we use three levels of simulations to demonstrate that charged residues in the exit tunnel generate tensile forces that act on the P-site residue, which in turn changes the transition state barrier heights to peptide bond formation. We find that the forces generated by positive and negatively charged residues act in opposite directions, causing only the positively charged residues to stall, and that these forces increase as the length of the charged segment increases. Furthermore, we use ribosome profiling to show that the changes in translation speeds occur in vivo and that the largest slowdowns that occur when strings of positively charged residues are translated occur at the same locations as the largest forces measured in silico.

Pressure Tuning Studies of Four-Stranded Nucleic Acid Structures

“…The pressure behavior of several GQ structures has been investigated [ 14 , 26 , 46 , 51 , 61 , 62 , 63 , 64 , 65 , 66 ]. The studied sequences are listed in Table 1 , while the main results are summarized in Table 2 .…”

“…Liu et al studied the same c-MYC sequence [ 64 ]. They predicted an elliptic phase boundary for their c-MYC variant, similar to that which was found in the case of several proteins [ 33 , 35 , 72 ].…”