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-Structure paper
Title | Tertiary structure of single-instant RNA molecule reveals folding landscape. |
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Journal, issue, pages | bioRxiv, Year 2023 |
Publish date | May 20, 2023 |
Authors | Jianfang Liu / Ewan K S McRae / Meng Zhang / Cody Geary / Ebbe Sloth Andersen / Gang Ren |
PubMed Abstract | The folding of RNA and protein molecules during their synthesis is a crucial self-assembly process that nature employs to convert genetic information into the complex molecular machinery that ...The folding of RNA and protein molecules during their synthesis is a crucial self-assembly process that nature employs to convert genetic information into the complex molecular machinery that supports life. Misfolding events are the cause of several diseases, and the folding pathway of central biomolecules, such as the ribosome, is strictly regulated by programmed maturation processes and folding chaperones. However, the dynamic folding processes are challenging to study because current structure determination methods heavily rely on averaging, and existing computational methods do not efficiently simulate non-equilibrium dynamics. Here we utilize individual-particle cryo-electron tomography (IPET) to investigate the folding landscape of a rationally designed RNA origami 6-helix bundle that undergoes slow maturation from a "young" to "mature" conformation. By optimizing the IPET imaging and electron dose conditions, we obtain 3D reconstructions of 120 individual particles at resolutions ranging from 23-35 Å, enabling us first-time to observe individual RNA helices and tertiary structures without averaging. Statistical analysis of 120 tertiary structures confirms the two main conformations and suggests a possible folding pathway driven by helix-helix compaction. Studies of the full conformational landscape reveal both trapped states, misfolded states, intermediate states, and fully compacted states. The study provides novel insight into RNA folding pathways and paves the way for future studies of the energy landscape of molecular machines and self-assembly processes. |
External links | bioRxiv / PubMed:37292713 / PubMed Central |
Methods | EM (tomography) |
Resolution | 24.0 - 33.0 Å |
Structure data | EMDB-25238: Tertiary structure of an individual particle of self-folding RNA polymer (particle #129) EMDB-25239: Tertiary structure of an individual particle of self-folding RNA polymer (particle #130) EMDB-25240: Tertiary structure of an individual particle of self-folding RNA polymer (particle #131) EMDB-25241: Tertiary structure of an individual particle of self-folding RNA polymer (particle #147) EMDB-25242: Tertiary structure of an individual particle of self-folding RNA polymer (particle #148) EMDB-25243: Tertiary structure of an individual particle of self-folding RNA polymer (particle #149) EMDB-25244: Tertiary structure of an individual particle of self-folding RNA polymer (particle #150) EMDB-25245: Tertiary structure of an individual particle of self-folding RNA polymer (particle #151) EMDB-25270: Tertiary structure of an individual particle of self-folding RNA polymer (particle #144) EMDB-25271: Tertiary structure of an individual particle of self-folding RNA polymer (particle #145) EMDB-25272: Tertiary structure of an individual particle of self-folding RNA polymer (particle #146) EMDB-25273: Tertiary structure of an individual particle of self-folding RNA polymer (particle #036) EMDB-25274: Tertiary structure of an individual particle of self-folding RNA polymer (particle #037) EMDB-25275: Tertiary structure of an individual particle of self-folding RNA polymer (particle #038) EMDB-25276: Tertiary structure of an individual particle of self-folding RNA polymer (particle #039) EMDB-25277: Tertiary structure of an individual particle of self-folding RNA polymer (particle #040) EMDB-25278: Tertiary structure of an individual particle of self-folding RNA polymer (particle #041) EMDB-25279: Tertiary structure of an individual particle of self-folding RNA polymer (particle #043) EMDB-25280: Tertiary structure of an individual particle of self-folding RNA polymer (particle #044) EMDB-25281: Tertiary structure of an individual particle of self-folding RNA polymer (particle #045) EMDB-25282: Tertiary structure of an individual particle of self-folding RNA polymer (particle #047) EMDB-25283: Tertiary structure of an individual particle of self-folding RNA polymer (particle #048) EMDB-25284: Tertiary structure of an individual particle of self-folding RNA polymer (particle #049) EMDB-25285: Tertiary structure of an individual particle of self-folding RNA polymer (particle #050) EMDB-25286: Tertiary structure of an individual particle of self-folding RNA polymer (particle #051) EMDB-25287: Tertiary structure of an individual particle of self-folding RNA polymer (particle #052) EMDB-25288: Tertiary structure of an individual particle of self-folding RNA polymer (particle #053) EMDB-25289: Tertiary structure of an individual particle of self-folding RNA polymer (particle #054) EMDB-25290: Tertiary structure of an individual particle of self-folding RNA polymer (particle #055) EMDB-25291: Tertiary structure of an individual particle of self-folding RNA polymer (particle #056) EMDB-25292: Tertiary structure of an individual particle of self-folding RNA polymer (particle #057) EMDB-25293: Tertiary structure of an individual particle of self-folding RNA polymer (particle #058) EMDB-25294: Tertiary structure of an individual particle of self-folding RNA polymer (particle #059) EMDB-25295: Tertiary structure of an individual particle of self-folding RNA polymer (particle #060) EMDB-25296: Tertiary structure of an individual particle of self-folding RNA polymer (particle #061) EMDB-25297: Tertiary structure of an individual particle of self-folding RNA polymer (particle #062) EMDB-25298: Tertiary structure of an individual particle of self-folding RNA polymer (particle #063) EMDB-25299: Tertiary structure of an individual particle of self-folding RNA polymer (particle #064) EMDB-25300: Tertiary structure of an individual particle of self-folding RNA polymer (particle #065) EMDB-25301: Tertiary structure of an individual particle of self-folding RNA polymer (particle #066) EMDB-25302: Tertiary structure of an individual particle of self-folding RNA polymer (particle #067) EMDB-25352: Tertiary structure of an individual particle of self-folding RNA polymer (particle #119) EMDB-25353: Tertiary structure of an individual particle of self-folding RNA polymer (particle #120) EMDB-25355: Tertiary structure of an individual particle of self-folding RNA polymer (particle #083) EMDB-25356: Tertiary structure of an individual particle of self-folding RNA polymer (particle #042) EMDB-25357: Tertiary structure of an individual particle of self-folding RNA polymer (particle #046) EMDB-40353: Tertiary structure of an individual particle of self-folding RNA polymer (particle #001) EMDB-40356: Tertiary structure of an individual particle of self-folding RNA polymer (particle #002) EMDB-40357: Tertiary structure of an individual particle of self-folding RNA polymer (particle #003) EMDB-40358: Tertiary structure of an individual particle of self-folding RNA polymer (particle #004) EMDB-40359: Tertiary structure of an individual particle of self-folding RNA polymer (particle #005) EMDB-40360: Tertiary structure of an individual particle of self-folding RNA polymer (particle #006) EMDB-40361: Tertiary structure of an individual particle of self-folding RNA polymer (particle #007) EMDB-40362: Tertiary structure of an individual particle of self-folding RNA polymer (particle #008) EMDB-40363: Tertiary structure of an individual particle of self-folding RNA polymer (particle #009) EMDB-40364: Tertiary structure of an individual particle of self-folding RNA polymer (particle #010) |
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