7A5P

Human C Complex Spliceosome - Medium-resolution PERIPHERY

Summary for 7A5P

• Entry DOI: 10.2210/pdb7a5p/pdb
• EMDB information: 11570 11571 11572 11573 11574
• Descriptor: U2 snRNA, Cell division cycle 5-like protein, Pre-mRNA-splicing factor SYF1, ... (38 entities in total)
• Functional Keywords: human c complex, spliceosome, hc, human step 1 spliceosome, splicing
• Biological source: Homo sapiens; More
• Total number of polymer chains: 48
• Total formula weight: 3093739.62

Authors

Bertram, K.,Kastner, B. (deposition date: 2020-08-21, release date: 2020-10-14, Last modification date: 2024-10-09)

Primary citation

Bertram, K.,El Ayoubi, L.,Dybkov, O.,Agafonov, D.E.,Will, C.L.,Hartmuth, K.,Urlaub, H.,Kastner, B.,Stark, H.,Luhrmann, R.
Structural Insights into the Roles of Metazoan-Specific Splicing Factors in the Human Step 1 Spliceosome.
Mol.Cell, 80:127-139.e6, 2020

PubMed Abstract: Human spliceosomes contain numerous proteins absent in yeast, whose functions remain largely unknown. Here we report a 3D cryo-EM structure of the human spliceosomal C complex at 3.4 Å core resolution and 4.5-5.7 Å at its periphery, and aided by protein crosslinking we determine its molecular architecture. Our structure provides additional insights into the spliceosome's architecture between the catalytic steps of splicing, and how proteins aid formation of the spliceosome's catalytically active RNP (ribonucleoprotein) conformation. It reveals the spatial organization of the metazoan-specific proteins PPWD1, WDR70, FRG1, and CIR1 in human C complexes, indicating they stabilize functionally important protein domains and RNA structures rearranged/repositioned during the B to C transition. Structural comparisons with human B, C, and P complexes reveal an intricate cascade of RNP rearrangements during splicing catalysis, with intermediate RNP conformations not found in yeast, and additionally elucidate the structural basis for the sequential recruitment of metazoan-specific spliceosomal proteins.

PubMed: 33007253
DOI: 10.1016/j.molcel.2020.09.012

Experimental method

ELECTRON MICROSCOPY (5 Å)