5O9Z
Cryo-EM structure of a pre-catalytic human spliceosome primed for activation (B complex)
Summary for 5O9Z
| Entry DOI | 10.2210/pdb5o9z/pdb |
| EMDB information | 3766 |
| Descriptor | Pre-mRNA-processing-splicing factor 8, Thioredoxin-like protein 4A, Microfibrillar-associated protein 1, ... (43 entities in total) |
| Functional Keywords | spliceosome, pre-mrna splicing, macromolecular complex, splicing |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 57 |
| Total formula weight | 2389149.82 |
| Authors | Bertram, K.,Kastner, B. (deposition date: 2017-06-20, release date: 2017-08-16, Last modification date: 2018-10-24) |
| Primary citation | Bertram, K.,Agafonov, D.E.,Dybkov, O.,Haselbach, D.,Leelaram, M.N.,Will, C.L.,Urlaub, H.,Kastner, B.,Luhrmann, R.,Stark, H. Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation. Cell, 170:701-713.e11, 2017 Cited by PubMed Abstract: 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. PubMed: 28781166DOI: 10.1016/j.cell.2017.07.011 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.5 Å) |
Structure validation
Download full validation report
