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PDBsum entry 6dnh
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RNA binding protein/RNA
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PDB id
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6dnh
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1177 a.a.
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376 a.a.
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117 a.a.
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References listed in PDB file
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Key reference
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Title
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Molecular basis for the recognition of the human aauaaa polyadenylation signal.
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Authors
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Y.Sun,
Y.Zhang,
K.Hamilton,
J.L.Manley,
Y.Shi,
T.Walz,
L.Tong.
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Ref.
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Proc Natl Acad Sci U S A, 2018,
115,
E1419.
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PubMed id
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Abstract
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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.
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