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-Structure paper
タイトル | Structural Insights into the Roles of Metazoan-Specific Splicing Factors in the Human Step 1 Spliceosome. |
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ジャーナル・号・ページ | Mol Cell, Vol. 80, Issue 1, Page 127-139.e6, Year 2020 |
掲載日 | 2020年10月1日 |
著者 | Karl Bertram / Leyla El Ayoubi / Olexandr Dybkov / Dmitry E Agafonov / Cindy L Will / Klaus Hartmuth / Henning Urlaub / Berthold Kastner / Holger Stark / Reinhard Lührmann / |
PubMed 要旨 | Human spliceosomes contain numerous proteins absent in yeast, whose functions remain largely unknown. Here we report a 3D cryo-EM structure of the human spliceosomal C complex at 3.4 Å core ...Human spliceosomes contain numerous proteins absent in yeast, whose functions remain largely unknown. Here we report a 3D cryo-EM structure of the human spliceosomal C complex at 3.4 Å core resolution and 4.5-5.7 Å at its periphery, and aided by protein crosslinking we determine its molecular architecture. Our structure provides additional insights into the spliceosome's architecture between the catalytic steps of splicing, and how proteins aid formation of the spliceosome's catalytically active RNP (ribonucleoprotein) conformation. It reveals the spatial organization of the metazoan-specific proteins PPWD1, WDR70, FRG1, and CIR1 in human C complexes, indicating they stabilize functionally important protein domains and RNA structures rearranged/repositioned during the B to C transition. Structural comparisons with human B, C, and P complexes reveal an intricate cascade of RNP rearrangements during splicing catalysis, with intermediate RNP conformations not found in yeast, and additionally elucidate the structural basis for the sequential recruitment of metazoan-specific spliceosomal proteins. |
リンク | Mol Cell / PubMed:33007253 |
手法 | EM (単粒子) |
解像度 | 3.4 - 5.7 Å |
構造データ | EMDB-11569, PDB-6zym: EMDB-11570: Human C Complex Spliceosome - MultiBody refined EXTENDED CORE EMDB-11571: EMDB-11572: EMDB-11573: EMDB-11574: |
化合物 | ChemComp-MG: ChemComp-IHP: ChemComp-GTP: ChemComp-ZN: |
由来 |
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キーワード | SPLICING / human C complex / spliceosome / hC / human step 1 spliceosome |