6QX9

Structure of a human fully-assembled precatalytic spliceosome (pre-B complex).

This is a non-PDB format compatible entry.

Summary for 6QX9

• Entry DOI: 10.2210/pdb6qx9/pdb
• Related: 6QW6
• EMDB information: 4658 4665
• Descriptor: U1 snRNA, U4/U6 small nuclear ribonucleoprotein Prp31, Small nuclear ribonucleoprotein Sm D1, ... (54 entities in total)
• Functional Keywords: rnp complex, splicing, rna, protein, spliceosome
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 71
• Total formula weight: 2871622.27

Authors

Charenton, C.,Wilkinson, M.E.,Nagai, K. (deposition date: 2019-03-07, release date: 2019-04-17, Last modification date: 2024-11-13)

Primary citation

Charenton, C.,Wilkinson, M.E.,Nagai, K.
Mechanism of 5' splice site transfer for human spliceosome activation.
Science, 364:362-367, 2019

PubMed Abstract: The prespliceosome, comprising U1 and U2 small nuclear ribonucleoproteins (snRNPs) bound to the precursor messenger RNA 5' splice site (5'SS) and branch point sequence, associates with the U4/U6.U5 tri-snRNP to form the fully assembled precatalytic pre-B spliceosome. Here, we report cryo-electron microscopy structures of the human pre-B complex captured before U1 snRNP dissociation at 3.3-angstrom core resolution and the human tri-snRNP at 2.9-angstrom resolution. U1 snRNP inserts the 5'SS-U1 snRNA helix between the two RecA domains of the Prp28 DEAD-box helicase. Adenosine 5'-triphosphate-dependent closure of the Prp28 RecA domains releases the 5'SS to pair with the nearby U6 ACAGAGA-box sequence presented as a mobile loop. The structures suggest that formation of the 5'SS-ACAGAGA helix triggers remodeling of an intricate protein-RNA network to induce Brr2 helicase relocation to its loading sequence in U4 snRNA, enabling Brr2 to unwind the U4/U6 snRNA duplex to allow U6 snRNA to form the catalytic center of the spliceosome.

PubMed: 30975767
DOI: 10.1126/science.aax3289

Experimental method

ELECTRON MICROSCOPY (3.28 Å)