8e3i | pdb_00008e3i

CRYO-EM STRUCTURE OF the human MPSF IN COMPLEX WITH THE AUUAAA poly(A) signal

spinqualitylabelsall models 8e3i, resolution 2.53Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8e3i is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CPSF1_HUMAN Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. This subunit is involved in the RNA recognition step of the polyadenylation reaction. Publication Abstract from PubMed The polyadenylation signal (PAS) is a key sequence element for 3'-end cleavage and polyadenylation of messenger RNA precursors (pre-mRNAs). This hexanucleotide motif is recognized by the mammalian polyadenylation specificity factor (mPSF), consisting of CPSF160, WDR33, CPSF30, and Fip1 subunits. Recent studies have revealed how the AAUAAA PAS, the most frequently observed PAS, is recognized by mPSF. We report here the structure of human mPSF in complex with the AUUAAA PAS, the second most frequently identified PAS. Conformational differences are observed for the A1 and U2 nucleotides in AUUAAA compared to the A1 and A2 nucleotides in AAUAAA, while the binding modes of the remaining 4 nt are essentially identical. The 5' phosphate of U2 moves by 2.6 A and the U2 base is placed near the six-membered ring of A2 in AAUAAA, where it makes two hydrogen bonds with zinc finger 2 (ZF2) of CPSF30, which undergoes conformational changes as well. We also attempted to determine the binding modes of two rare PAS hexamers, AAGAAA and GAUAAA, but did not observe the RNA in the cryo-electron microscopy density. The residues in CPSF30 (ZF2 and ZF3) and WDR33 that recognize PAS are disordered in these two structures. Molecular basis for the recognition of the AUUAAA polyadenylation signal by mPSF.,Gutierrez PA, Wei J, Sun Y, Tong L RNA. 2022 Nov;28(11):1534-1541. doi: 10.1261/rna.079322.122. Epub 2022 Sep 6. PMID:36130077 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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