Visualizing RNA conformational and architectural heterogeneity in solution

被引:33
|
作者
Ding, Jienyu [1 ]
Lee, Yun-Tzai [1 ]
Bhandari, Yuba [1 ]
Schwieters, Charles D. [2 ]
Fan, Lixin [3 ]
Yu, Ping [1 ]
Tarosov, Sergey G. [4 ]
Stagno, Jason R. [1 ]
Ma, Buyong [5 ]
Nussinov, Ruth [5 ]
Rein, Alan [6 ]
Zhang, Jinwei [7 ]
Wang, Yun-Xing [1 ]
机构
[1] NCI, Ctr Struct Biol, Prot Nucl Acid Interact Sect, Frederick, MD 21702 USA
[2] Natl Inst Diabet & Digest & Kidney Dis, NIH, Computat Biomol Magnet Resonance Core, Bethesda, MD 20892 USA
[3] Small Angle Xray Scattering Core Facil, NIH, Natl Canc Inst, Basic Sci Program,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA
[4] NCI, Ctr Struct Biol, Biophys Resource, Frederick, MD 21702 USA
[5] NCI, Computat Struct Biol Sect, Frederick Natl Lab Canc Res Lab Canc Immunometab, Frederick, MD 21702 USA
[6] NCI, HIV Dynam & Replicat Program, Retrovirus Assembly Sect, Frederick, MD 21702 USA
[7] Natl Inst Diabet & Digest & Kidney Dis, Lab Mol Biol, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
ATOMIC-FORCE MICROSCOPY; VITAMIN-B-12; METABOLISM; RESOLUTION; DYNAMICS; RIBOSWITCH; SCATTERING; MODELS;
D O I
10.1038/s41467-023-36184-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
RNA flexibility is reflected in its heterogeneous conformation. Through direct visualization using atomic force microscopy (AFM) and the adenosylcobalamin riboswitch aptamer domain as an example, we show that a single RNA sequence folds into conformationally and architecturally heterogeneous structures under near-physiological solution conditions. Recapitulated 3D topological structures from AFM molecular surfaces reveal that all conformers share the same secondary structural elements. Only a population-weighted cohort, not any single conformer, including the crystal structure, can account for the ensemble behaviors observed by small-angle X-ray scattering (SAXS). All conformers except one are functionally active in terms of ligand binding. Our findings provide direct visual evidence that the sequence-structure relationship of RNA under physiologically relevant solution conditions is more complex than the one-to-one relationship for well-structured proteins. The direct visualization of conformational and architectural ensembles at the single-molecule level in solution may suggest new approaches to RNA structural analyses. RNA conformational heterogeneity is important to diverse functions. Here, the authors use AFM to directly visualize individual RNA molecules that are in various conformational states under near physiological solution conditions for the first time.
引用
收藏
页数:11
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