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Title | Structure and Conformational Dynamics of the Human Spliceosomal B Complex. |
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Journal, issue, pages | Cell, Vol. 172, Issue 3, Page 454-464.e11, Year 2018 |
Publish date | Jan 25, 2018 |
Authors | David Haselbach / Ilya Komarov / Dmitry E Agafonov / Klaus Hartmuth / Benjamin Graf / Olexandr Dybkov / Henning Urlaub / Berthold Kastner / Reinhard Lührmann / Holger Stark / |
PubMed Abstract | The spliceosome is a highly dynamic macromolecular complex that precisely excises introns from pre-mRNA. Here we report the cryo-EM 3D structure of the human B spliceosome at 3.4 Å resolution. In ...The spliceosome is a highly dynamic macromolecular complex that precisely excises introns from pre-mRNA. Here we report the cryo-EM 3D structure of the human B spliceosome at 3.4 Å resolution. In the B state, the spliceosome is activated but not catalytically primed, so that it is functionally blocked prior to the first catalytic step of splicing. The spliceosomal core is similar to the yeast B spliceosome; important differences include the presence of the RNA helicase aquarius and peptidyl prolyl isomerases. To examine the overall dynamic behavior of the purified spliceosome, we developed a principal component analysis-based approach. Calculating the energy landscape revealed eight major conformational states, which we refined to higher resolution. Conformational differences of the highly flexible structural components between these eight states reveal how spliceosomal components contribute to the assembly of the spliceosome, allowing it to generate a dynamic interaction network required for its subsequent catalytic activation. |
External links | Cell / PubMed:29361316 |
Methods | EM (single particle) |
Resolution | 3.4 - 16.0 Å |
Structure data | EMDB-4233: EMDB-4234: EMDB-4235: EMDB-4236: EMDB-4237: EMDB-4238: EMDB-4239: EMDB-4240: Human Bact spliceosome state 8 unmasked EMDB-4247: EMDB-4248: EMDB-4249: EMDB-4250: EMDB-4251: EMDB-4252: EMDB-4253: EMDB-4254: |
Chemicals | ChemComp-MG: ChemComp-IHP: ChemComp-GTP: ChemComp-ZN: ChemComp-ADP: |
Source |
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Keywords | SPLICING / spliceosome / human / HELA / BACT / dynamics |