5o9z

Cryo-EM structure of a pre-catalytic human spliceosome primed for activation (B complex)Cryo-EM structure of a pre-catalytic human spliceosome primed for activation (B complex)

5o9z, resolution 4.50Å Show:Asymmetric Unit Biological Assembly Structural highlights 5o9z is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.5Å Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease PRP8_HUMAN Defects in PRPF8 are the cause of retinitis pigmentosa type 13 (RP13) [MIM:600059. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP13 inheritance is autosomal dominant. [:] Function PRP8_HUMAN Central component of the spliceosome, which may play a role in aligning the pre-mRNA 5'- and 3'-exons for ligation. Interacts with U5 snRNA, and with pre-mRNA 5'-splice sites in B spliceosomes and 3'-splice sites in C spliceosomes. Publication Abstract from PubMed 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. Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation.,Bertram K, Agafonov DE, Dybkov O, Haselbach D, Leelaram MN, Will CL, Urlaub H, Kastner B, Luhrmann R, Stark H Cell. 2017 Aug 10;170(4):701-713.e11. doi: 10.1016/j.cell.2017.07.011. Epub 2017 , Aug 3. PMID:28781166 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nucleoprotein 3D structures Pre-mRNA splicing factors 3D structures Sm-like protein 3D structures