Download MendeleyCryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation.
Bertram, K., Agafonov, D.E., Dybkov, O., Haselbach, D., Leelaram, M.N., Will, C.L., Urlaub, H., Kastner, B., Luhrmann, R., Stark, H.(2017) Cell 170: 701-713.e11
- PubMed: 28781166
- DOI: https://doi.org/10.1016/j.cell.2017.07.011
- Primary Citation of Related Structures:
5O9Z - 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.
Organizational Affiliation:
Department of Structural Dynamics, MPI for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
