title: Dynamics Correlation Network for Allosteric Switching of PreQ1 Riboswitch.
abstract: Riboswitches are a class of metabolism control elements mostly found in bacteria. Due to their fundamental importance in bacteria gene regulation, riboswitches have been proposed as antibacterial drug targets. Prequeuosine (preQ1) is the last free precursor in the biosynthetic pathway of queuosine that is crucial for translation efficiency and fidelity. However, the regulation mechanism for the preQ1 riboswitch remains unclear. Here we constructed fluctuation correlation network based on all-atom molecular dynamics simulations to reveal the regulation mechanism. The results suggest that the correlation network in the bound riboswitch is distinctly different from that in the apo riboswitch. The community network indicates that the information freely transfers from the binding site of preQ1 to the expression platform of the P3 helix in the bound riboswitch and the P3 helix is a bottleneck in the apo riboswitch. Thus, a hypothesis of "preQ1-binding induced allosteric switching" is proposed to link riboswitch and translation regulation. The community networks of mutants support this hypothesis. Finally, a possible allosteric pathway of A50-A51-A52-U10-A11-G12-G56 was also identified based on the shortest path algorithm and confirmed by mutations and network perturbation. The novel fluctuation network analysis method can be used as a general strategy in studies of riboswitch structure-function relationship.
authors.affiliation: State Key Laboratory of Microbial metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Microbial metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Microbial metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, China.
authors.forename: Jinmai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Microbial metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Departments of Molecular Biology and Biochemistry, Chemical Engineering and Materials Science, Biomedical Engineering, University of California, Irvine, California 92697-3900, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Microbial metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, China.|Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 200235, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Chen
mesh_terms: D000494:Allosteric Regulation; D001419:Bacteria / Q000737:chemistry* / Q000235:genetics; D009690:Nucleic Acid Conformation; D058928:Riboswitch
chemical_list: D058928:Riboswitch