7Q4O

Substrate-bound A-like U2 snRNP

Summary for 7Q4O

• Entry DOI: 10.2210/pdb7q4o/pdb
• Related: 7Q3L
• EMDB information: 13811
• Descriptor: Splicing factor 3A subunit 2, BPS oligo, ZINC ION, ... (12 entities in total)
• Functional Keywords: splicing, snrnp, spliceosome, nuclear protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 593518.44

Authors

Tholen, J.,Galej, W.P. (deposition date: 2021-11-01, release date: 2022-03-30, Last modification date: 2024-07-17)

Primary citation

Tholen, J.,Razew, M.,Weis, F.,Galej, W.P.
Structural basis of branch site recognition by the human spliceosome.
Science, 375:50-57, 2022

PubMed Abstract: Recognition of the intron branch site (BS) by the U2 small nuclear ribonucleoprotein (snRNP) is a critical event during spliceosome assembly. In mammals, BS sequences are poorly conserved, and unambiguous intron recognition cannot be achieved solely through a base-pairing mechanism. We isolated human 17 U2 snRNP and reconstituted in vitro its adenosine 5´-triphosphate (ATP)–dependent remodeling and binding to the pre–messenger RNA substrate. We determined a series of high-resolution (2.0 to 2.2 angstrom) structures providing snapshots of the BS selection process. The substrate-bound U2 snRNP shows that SF3B6 stabilizes the BS:U2 snRNA duplex, which could aid binding of introns with poor sequence complementarity. ATP-dependent remodeling uncoupled from substrate binding captures U2 snRNA in a conformation that competes with BS recognition, providing a selection mechanism based on branch helix stability.

PubMed: 34822310
DOI: 10.1126/science.abm4245

Experimental method

ELECTRON MICROSCOPY (2.1 Å)