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-Structure paper
| タイトル | Structural Dynamics of RNA Polymerase II During Nucleotide Addition Cycle. |
|---|---|
| ジャーナル・号・ページ | bioRxiv, Year 2026 |
| 掲載日 | 2026年6月5日 |
著者 | Gangshun Yi / Qingrong Li / Hannah Holmberg / Shisheng Li / Daniel K Clare / Dong Wang / Peijun Zhang / ![]() |
| PubMed 要旨 | RNA polymerase II (RNAPII) drives gene expression through iterative nucleotide addition cycles (NACs) comprising translocation, substrate binding, and catalysis. The lack of pre-catalysis and post- ...RNA polymerase II (RNAPII) drives gene expression through iterative nucleotide addition cycles (NACs) comprising translocation, substrate binding, and catalysis. The lack of pre-catalysis and post-catalysis intermediates has precluded a complete mechanistic understanding of the NAC. Here we present 43 cryo-EM structures capturing distinct stages of the RNAPII elongation complex (EC) NAC, including previously intractable transition intermediates. We establish a continuous spectrum of RNAPII EC structural dynamics during the NAC, which can be divided into two coordinated phases: a substrate-induced EC tightening phase and a post-catalysis EC relaxation phase. For the substrate-induced EC tightening phase, the substrate binding initiates allosteric conformational changes across the entire RNAPII EC, including TL folding, funnel closure, clamp closure, transcription bubble ordering, and precise alignment of the RNA 3'-end with substrate to form a catalysis-competent configuration. For the post-catalysis EC relaxation phase, we captured the long-sought, short-lived post-catalysis product state and identified a series of intermediates that reveal a reverse conformational transition that facilitates rapid translocation. Together, our findings define a comprehensive structural and dynamic framework for RNAPII NAC, yielding a "molecular movie" of RNAPII in action and revealing a fundamental principle by which the enzyme balances speed and fidelity through coordinated conformational dynamics. |
リンク | bioRxiv / PubMed:42282700 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.54 - 4.28 Å |
| 構造データ | ![]() EMDB-54677: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class A (frame1) ![]() EMDB-54679: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class E (frame9) ![]() EMDB-54680: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class D (frame8) ![]() EMDB-54681: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class C (frame7) ![]() EMDB-54682: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class B (frame4) ![]() EMDB-54683: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class F (frame 10) ![]() EMDB-54684: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class G (frame 13) ![]() EMDB-54685: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class H (frame 15) ![]() EMDB-54686: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class I (frame 17) ![]() EMDB-54687: CryoEM map of Yeast RNA polymerase II elongation complex with ATP-3D class J (frame 20) EMDB-54704, PDB-9say: ![]() EMDB-54705: CryoEM map of Yeast RNA polymerase II elongation complex apo-state-I-A ![]() EMDB-54706: CryoEM map of Yeast RNA polymerase II elongation complex apo-state-I-B EMDB-54707, PDB-9saz: EMDB-54708, PDB-9sb0: EMDB-54709, PDB-9sb1: EMDB-54710, PDB-9sb2: EMDB-54711, PDB-9sb3: EMDB-54712, PDB-9sb4: EMDB-54713, PDB-9sb5: EMDB-54730, PDB-9sbl: EMDB-54731, PDB-9sbm: EMDB-54732, PDB-9sbn: EMDB-54733, PDB-9sbo: EMDB-54734, PDB-9sbp: EMDB-54735, PDB-9sbq: EMDB-54736, PDB-9sbr: EMDB-54737, PDB-9sbs: EMDB-54738, PDB-9sbt: EMDB-54739, PDB-9sbu: EMDB-54740, PDB-9sbv: EMDB-54741, PDB-9sbw: EMDB-54742, PDB-9sbx: EMDB-54743, PDB-9sby: EMDB-54744, PDB-9sbz: EMDB-54745, PDB-9sc0: EMDB-54746, PDB-9sc1: EMDB-54747, PDB-9sc2: EMDB-54748, PDB-9sc3: EMDB-54749, PDB-9sc4: EMDB-57322, PDB-29rf: EMDB-57673, PDB-30ep: EMDB-57676, PDB-30es: |
| 化合物 | ![]() ChemComp-ZN: ![]() ChemComp-MG: ![]() ChemComp-GTP: ![]() ChemComp-ATP: ![]() ChemComp-PPV: |
| 由来 |
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キーワード | TRANSCRIPTION / CryoEM / RNA Polymerase |
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