3JCR

3D structure determination of the human*U4/U6.U5* tri-snRNP complex

Summary for 3JCR

• Entry DOI: 10.2210/pdb3jcr/pdb
• EMDB information: 6581
• Descriptor: hPrp6, SmD2, SmD3, ... (29 entities in total)
• Functional Keywords: snrnp, splicing, spliceosome, human
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 36
• Total formula weight: 1544413.44

Authors

Agafonov, D.E.,Kastner, B.,Dybkov, O.,Hofele, R.V.,Liu, W.T.,Urlaub, H.,Luhrmann, R.,Stark, H. (deposition date: 2016-01-21, release date: 2016-03-09, Last modification date: 2024-02-21)

Primary citation

Agafonov, D.E.,Kastner, B.,Dybkov, O.,Hofele, R.V.,Liu, W.T.,Urlaub, H.,Luhrmann, R.,Stark, H.
Molecular architecture of the human U4/U6.U5 tri-snRNP.
Science, 351:1416-1420, 2016

PubMed Abstract: The U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri-snRNP at a resolution of 7 angstroms using single-particle cryo-electron microscopy (cryo-EM). We fit all known high-resolution structures of tri-snRNP components into the EM density map and validated them by protein cross-linking. Our model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the ubiquitin C-terminal hydrolase-like protein Sad1 likely tethers the helicase Brr2 to its preactivation position. Comparison of our model with cryo-EM three-dimensional structures of the Saccharomyces cerevisiae tri-snRNP and Schizosaccharomyces pombe spliceosome indicates that Brr2 undergoes a marked conformational change during spliceosome activation, and that the scaffolding protein Prp8 is also rearranged to accommodate the spliceosome's catalytic RNA network.

PubMed: 26912367
DOI: 10.1126/science.aad2085

Experimental method

ELECTRON MICROSCOPY (7 Å)