2023-06-22 レンセラー工科大学 (RPI)
◆最近の研究では、ロイヤー教授と彼女のチームは高圧下でヒトの転送リボ核酸(tRNA)の構造ダイナミクスを調べました。高圧により、通常は非常に低いレベルで存在するtRNAの励起状態の割合が増加し、tRNAの機能について新たな洞察が得られました。特にHIV感染にも関与している可能性が示唆されています。
◆この研究は、HIVの感染拡大に関する理解を深めることにつながる可能性があります。また、地球上の80%以上の微生物の生息地が高圧下に存在するため、高圧環境での生物分子の機能に関する理解は、より堅牢で活性の高い生物分子の開発につながる可能性があります。
<関連情報>
- https://news.rpi.edu/content/2023/06/22/rensselaer-researcher-uses-pressure-understand-rna-dynamics
- https://www.pnas.org/doi/10.1073/pnas.2215556120
圧力によってtRNALys3が励起されたコンフォメーション状態になる Pressure pushes tRNALys3 into excited conformational states
Jinqiu Wang,Tejaswi Koduru,Balasubramanian Harish,Scott A. McCallum ,Kevin P. Larsen,Karishma S. Patel,Edgar V. Peters,Richard E. Gillilan,Elisabetta V. Puglisi,Joseph D. Puglisi,George Makhatadze and Catherine A. Royer
Proceedings of the National Academy of Sciences Published:June 20, 2023
DOI:https://doi.org/10.1073/pnas.2215556120
Significance
Conformational dynamics and high-energy excited states play important roles in RNA function, underscoring the importance of their detailed structural and energetic characterization. High-pressure perturbation leads to an increase in the population of RNA-excited states. Combining high-pressure, 2D-NMR, small-angle X-ray scattering, and computation allowed evaluation of the stability and structural properties of excited states of human tRNALys3.
Abstract
Conformational dynamics play essential roles in RNA function. However, detailed structural characterization of excited states of RNA remains challenging. Here, we apply high hydrostatic pressure (HP) to populate excited conformational states of tRNALys3, and structurally characterize them using a combination of HP 2D-NMR, HP-SAXS (HP-small-angle X-ray scattering), and computational modeling. HP-NMR revealed that pressure disrupts the interactions of the imino protons of the uridine and guanosine U–A and G–C base pairs of tRNALys3. HP-SAXS profiles showed a change in shape, but no change in overall extension of the transfer RNA (tRNA) at HP. Configurations extracted from computational ensemble modeling of HP-SAXS profiles were consistent with the NMR results, exhibiting significant disruptions to the acceptor stem, the anticodon stem, and the D-stem regions at HP. We propose that initiation of reverse transcription of HIV RNA could make use of one or more of these excited states.
