2I7V

Structure of Human CPSF-73

Summary for 2I7V

• Entry DOI: 10.2210/pdb2i7v/pdb
• Related: 2I7T 2I7X
• Descriptor: Cleavage and polyadenylation specificity factor 73 kDa subunit, ZINC ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: polyadenylation, metallo-b-lactamase, pre-mrna processing, artemis, v(d)j recombination, double-strand break repair, hydrolase, rna binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q9UKF6
• Total number of polymer chains: 1
• Total formula weight: 52660.61

Authors

Mandel, C.R.,Zhang, H.,Tong, L. (deposition date: 2006-08-31, release date: 2007-01-30, Last modification date: 2024-02-21)

Primary citation

Mandel, C.R.,Kaneko, S.,Zhang, H.,Gebauer, D.,Vethantham, V.,Manley, J.L.,Tong, L.
Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.
Nature, 444:953-956, 2006

PubMed Abstract: Most eukaryotic messenger RNA precursors (pre-mRNAs) undergo extensive maturational processing, including cleavage and polyadenylation at the 3'-end. Despite the characterization of many proteins that are required for the cleavage reaction, the identity of the endonuclease is not known. Recent analyses indicated that the 73-kDa subunit of cleavage and polyadenylation specificity factor (CPSF-73) might be the endonuclease for this and related reactions, although no direct data confirmed this. Here we report the crystal structures of human CPSF-73 at 2.1 A resolution, complexed with zinc ions and a sulphate that might mimic the phosphate group of the substrate, and the related yeast protein CPSF-100 (Ydh1) at 2.5 A resolution. Both CPSF-73 and CPSF-100 contain two domains, a metallo-beta-lactamase domain and a novel beta-CASP (named for metallo-beta-lactamase, CPSF, Artemis, Snm1, Pso2) domain. The active site of CPSF-73, with two zinc ions, is located at the interface of the two domains. Purified recombinant CPSF-73 possesses RNA endonuclease activity, and mutations that disrupt zinc binding in the active site abolish this activity. Our studies provide the first direct experimental evidence that CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.

PubMed: 17128255
DOI: 10.1038/nature05363

Experimental method

X-RAY DIFFRACTION (2.1 Å)