The conformational space of RNase P RNA in solution

• 成果类型: Article
• 署名作者: Lee, Yun-Tzai; Degenhardt, Maximilia F. S.; Skeparnias, Ilias; Degenhardt, Hermann F.; Bhandari, Yuba R.; Yu, Ping; Stagno, Jason R.; Fan, Lixin; Zhang, Jinwei; Wang, Yun-Xing
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3254
• DOI: 10.1038/s41586-024-08336-6
• 发表日期: 2025-01-30
• 关键词: ribonuclease-p; single-molecule; escherichia-coli; binding-sites; SCATTERING; sequence; domain; RESOLUTION; proteins; DYNAMICS

摘要

RNA conformational diversity has fundamental biological roles1, 2, 3, 4-5, but direct visualization of its full conformational space in solution has not been possible using traditional biophysical techniques. Using solution atomic force microscopy, a deep neural network and statistical analyses, we show that the ribonuclease P (RNase P) RNA adopts heterogeneous conformations consisting of a conformationally invariant core and highly flexible peripheral structural elements that sample a broad conformational space, with amplitudes as large as 20-60 & Aring; in a multitude of directions, with very low net energy cost. Increasing Mg2+ drives compaction and enhances enzymatic activity, probably by narrowing the conformational space. Moreover, analyses of the correlations and anticorrelations between spatial flexibility and sequence conservation suggest that the functional roles of both the structure and dynamics of key regions are embedded in the primary sequence. These findings reveal the structure-dynamics basis for the embodiment of both enzymatic precision and substrate promiscuity in the RNA component of the RNase P. Mapping the conformational space of the RNase P RNA demonstrates a new general approach to studying RNA structure and dynamics.