Abstract
Riboswitches are novel RNA regulatory elements. Each riboswitch molecule consists of two domains: aptamer and express platform. The three-dimensional (3D) structure of the aptamer domain, depending on ligand binding or not, controls that of the express platform, which then switches on or off transcriptional or translational process. Here we study the two types of preQ1 riboswitch aptamers from T. Tengcongensis (denoted as Tte preQ1 riboswitch for short below) and Bacillus subtilis (denoted as Bsu preQ1 riboswitch for short below), respectively. The free-state 3D structure of the Tte preQ1 riboswitch is the same as its bound state but the Bsu preQ1 riboswitch is not. Therefore, it is very interesting to investigate how these riboswitches realize their different regulation functions. We simulated the unfolding of these two aptamers through all-atom molecular dynamic simulation and found that they have similar unfolding or folding pathways and ligand-binding processes. The main difference between them is the folding intermediate states. The similarity and difference of their unfolding or folding dynamics may suggest their similar regulation mechanisms and account for their different functions, respectively. These results are also useful to understand the regulation mechanism of other riboswitches with free-state 3D structures similar to their bound states.
Highlights
Riboswitches are RNA regulatory elements that perform regulation functions through conformational switch between ligand-free and ligand-bound states [1,2,3]
It shows that the unfolding processes of both aptamers are similar: the P2 helix first loses its native contacts, the A-tract L3 loses its tertiary contacts with P1 region and the P1 stem unfolds
The order parameters are fractions of native contacts in the triplex P1-L3 and binding pocket region adding pseudoknot part P2-L1-L2. These free-energy landscapes further confirm the hierarchical unfolding pathways of the two aptamers. Both free-energy landscapes show two intermediate states: one has a flexible structure but with stable hairpin P1 and another is different for the two aptamers: for Bsu aptamer the intermediate state has a structure with opening P2 and binding pocket but stable triplex P1-L3; on the other hand, the intermediate state of Tte aptamer has a structure that is very close to the ligand-bound one but the P2 helix only has one of the base pairs G11:C30 remained and the base pairs C9:G33 has broken
Summary
Riboswitches are RNA regulatory elements that perform regulation functions through conformational switch between ligand-free and ligand-bound states [1,2,3]. The 3D structures of the ligand-bound states of many riboswitch aptamers have already been solved. The ligand-free 3D structures of some aptamers have been solved [4,5,6]. It is found that most of these free-state 3D structures adopt bound-like structures [7,8]. This proposes a question: How do these riboswitches perform regulation functions in free form?
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