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PDBsum entry 2po2
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Hydrolase/hydrolase
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PDB id
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2po2
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References listed in PDB file
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Key reference
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Title
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Insights into the mechanism of progressive RNA degradation by the archaeal exosome.
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Authors
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M.V.Navarro,
C.C.Oliveira,
N.I.Zanchin,
B.G.Guimarães.
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Ref.
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J Biol Chem, 2008,
283,
14120-14131.
[DOI no: ]
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PubMed id
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Abstract
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Initially identified in yeast, the exosome has emerged as a central component of
the RNA maturation and degradation machinery both in Archaea and eukaryotes.
Here we describe a series of high-resolution structures of the RNase PH ring
from the Pyrococcus abyssi exosome, one of them containing three 10-mer RNA
strands within the exosome catalytic chamber, and report additional nucleotide
interactions involving positions N5 and N7. Residues from all three Rrp41-Rrp42
heterodimers interact with a single RNA molecule, providing evidence for the
functional relevance of exosome ring-like assembly in RNA processivity.
Furthermore, an ADP-bound structure showed a rearrangement of nucleotide
interactions at site N1, suggesting a rationale for the elimination of
nucleoside diphosphate after catalysis. In combination with RNA degradation
assays performed with mutants of key amino acid residues, the structural data
presented here provide support for a model of exosome-mediated RNA degradation
that integrates the events involving catalytic cleavage, product elimination,
and RNA translocation. Finally, comparisons between the archaeal and human
exosome structures provide a possible explanation for the eukaryotic exosome
inability to catalyze phosphate-dependent RNA degradation.
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Figure 2.
FIGURE 2. P. abyssi exosome RNA recognition cleft. Rrp41
and Rrp42 subunits are colored in blue and light brown,
respectively. Heterodimers forming the hexameric ring are
assigned 1 to 3 and numbers in parentheses identify residues
from the same dimer. a, schematic representation of the N1 to N5
binding sites. Residues involved in RNA interaction are labeled
and shown in sticks. Residues mutated in this work are indicated
with a colored star. b, schematic representation showing the
RNA-exosome interactions in detail. c, stereo view of the N1
nucleotide binding site. The |F[o]| - |F[c]| electron density
map contoured at 4 is superposed on the
solvent atoms.
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Figure 7.
FIGURE 7. Schematic representation of the archaeal exosome
RNA processing mechanism. Inorganic phosphate and PB moiety of
the nucleoside diphosphate are represented in red. Green arrows
indicate structural rearrangements putatively involved in the
mechanism.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
14120-14131)
copyright 2008.
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