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-Structure paper
タイトル | Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation. |
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ジャーナル・号・ページ | Cell, Vol. 170, Issue 4, Page 701-713.e11, Year 2017 |
掲載日 | 2017年8月10日 |
著者 | Karl Bertram / Dmitry E Agafonov / Olexandr Dybkov / David Haselbach / Majety N Leelaram / Cindy L Will / Henning Urlaub / Berthold Kastner / Reinhard Lührmann / Holger Stark / |
PubMed 要旨 | Little is known about the spliceosome's structure before its extensive remodeling into a catalytically active complex. Here, we report a 3D cryo-EM structure of a pre-catalytic human spliceosomal B ...Little is known about the spliceosome's structure before its extensive remodeling into a catalytically active complex. Here, we report a 3D cryo-EM structure of a pre-catalytic human spliceosomal B complex. The U2 snRNP-containing head domain is connected to the B complex main body via three main bridges. U4/U6.U5 tri-snRNP proteins, which are located in the main body, undergo significant rearrangements during tri-snRNP integration into the B complex. These include formation of a partially closed Prp8 conformation that creates, together with Dim1, a 5' splice site (ss) binding pocket, displacement of Sad1, and rearrangement of Brr2 such that it contacts its U4/U6 substrate and is poised for the subsequent spliceosome activation step. The molecular organization of several B-specific proteins suggests that they are involved in negatively regulating Brr2, positioning the U6/5'ss helix, and stabilizing the B complex structure. Our results indicate significant differences between the early activation phase of human and yeast spliceosomes. |
リンク | Cell / PubMed:28781166 |
手法 | EM (単粒子) |
解像度 | 4.5 - 9.9 Å |
構造データ | EMDB-3766, PDB-5o9z: EMDB-3767: EMDB-3768: EMDB-3769: |
由来 |
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キーワード | SPLICING / Spliceosome / pre-mRNA splicing / macromolecular complex |