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PDBsum entry 6ej5
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RNA binding protein
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PDB id
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6ej5
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References listed in PDB file
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Key reference
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Title
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A conserved structural element in the RNA helicase upf1 regulates its catalytic activity in an isoform-Specific manner.
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Authors
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M.Gowravaram,
F.Bonneau,
J.Kanaan,
V.D.Maciej,
F.Fiorini,
S.Raj,
V.Croquette,
H.Le hir,
S.Chakrabarti.
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Ref.
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Nucleic Acids Res, 2018,
46,
2648-2659.
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PubMed id
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Abstract
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The RNA helicase UPF1 is a key component of the nonsense mediated mRNA decay
(NMD) pathway. Previous X-ray crystal structures of UPF1 elucidated the
molecular mechanisms of its catalytic activity and regulation. In this study, we
examine features of the UPF1 core and identify a structural element that adopts
different conformations in the various nucleotide- and RNA-bound states of UPF1.
We demonstrate, using biochemical and single molecule assays, that this
structural element modulates UPF1 catalytic activity and thereby refer to it as
the regulatory loop. Interestingly, there are two alternatively spliced isoforms
of UPF1 in mammals which differ only in the lengths of their regulatory loops.
The loop in isoform 1 (UPF11) is 11 residues longer than that of isoform 2. We
find that this small insertion in UPF11 leads to a two-fold increase in its
translocation and ATPase activities. To determine the mechanistic basis of this
differential catalytic activity, we have determined the X-ray crystal structure
of the helicase core of UPF11 in its apo-state. Our results point toward a novel
mechanism of regulation of RNA helicases, wherein alternative splicing leads to
subtle structural rearrangements within the protein that are critical to
modulate enzyme movements and catalytic activity.
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