6DNH

Cryo-EM structure of human CPSF-160-WDR33-CPSF-30-PAS RNA complex at 3.4 A resolution

Replaces:  6BLL

Summary for 6DNH

• Entry DOI: 10.2210/pdb6dnh/pdb
• EMDB information: 7112 7113 7114
• Descriptor: Cleavage and polyadenylation specificity factor subunit 1, pre-mRNA 3' end processing protein WDR33, Cleavage and polyadenylation specificity factor subunit 4, ... (5 entities in total)
• Functional Keywords: recognition of the aauaaa polyadenylation signal (pas), hoogsteen base pair, zinc finger, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 261824.65

Authors

Sun, Y.,Zhang, Y.,Hamilton, K.,Walz, T.,Tong, L. (deposition date: 2018-06-06, release date: 2018-06-27, Last modification date: 2024-03-13)

Primary citation

Sun, Y.,Zhang, Y.,Hamilton, K.,Manley, J.L.,Shi, Y.,Walz, T.,Tong, L.
Molecular basis for the recognition of the human AAUAAA polyadenylation signal.
Proc. Natl. Acad. Sci. U.S.A., 115:E1419-E1428, 2018

PubMed Abstract: Nearly all eukaryotic messenger RNA precursors must undergo cleavage and polyadenylation at their 3'-end for maturation. A crucial step in this process is the recognition of the AAUAAA polyadenylation signal (PAS), and the molecular mechanism of this recognition has been a long-standing problem. Here, we report the cryo-electron microscopy structure of a quaternary complex of human CPSF-160, WDR33, CPSF-30, and an AAUAAA RNA at 3.4-Å resolution. Strikingly, the AAUAAA PAS assumes an unusual conformation that allows this short motif to be bound directly by both CPSF-30 and WDR33. The A1 and A2 bases are recognized specifically by zinc finger 2 (ZF2) of CPSF-30 and the A4 and A5 bases by ZF3. Interestingly, the U3 and A6 bases form an intramolecular Hoogsteen base pair and directly contact WDR33. CPSF-160 functions as an essential scaffold and preorganizes CPSF-30 and WDR33 for high-affinity binding to AAUAAA. Our findings provide an elegant molecular explanation for how PAS sequences are recognized for mRNA 3'-end formation.

PubMed: 29208711
DOI: 10.1073/pnas.1718723115

Experimental method

ELECTRON MICROSCOPY (3.4 Å)