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PDBsum entry 3luj
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RNA binding protein
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PDB id
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3luj
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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RNA binding protein
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Title:
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Crystal structure of mid domain from hago2 in complex with ump
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Structure:
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Protein argonaute-2. Chain: a, b, c. Fragment: mid domain. Synonym: argonaute2, hago2, protein slicer, paz piwi domain protein, ppd, eukaryotic translation initiation factor 2c 2, eif-2c 2, eif2c 2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: eif2c2, ago2. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.80Å
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R-factor:
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0.197
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R-free:
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0.234
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Authors:
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F.Frank,N.Sonenberg,B.Nagar
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Key ref:
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F.Frank
et al.
(2010).
Structural basis for 5'-nucleotide base-specific recognition of guide RNA by human AGO2.
Nature,
465,
818-822.
PubMed id:
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Date:
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17-Feb-10
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Release date:
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26-May-10
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PROCHECK
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Headers
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References
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Q9UKV8
(AGO2_HUMAN) -
Protein argonaute-2 from Homo sapiens
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Seq:
Struc:
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859 a.a.
134 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Nature
465:818-822
(2010)
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PubMed id:
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Structural basis for 5'-nucleotide base-specific recognition of guide RNA by human AGO2.
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F.Frank,
N.Sonenberg,
B.Nagar.
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ABSTRACT
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MicroRNAs (miRNAs) mediate post-transcriptional gene regulation through
association with Argonaute proteins (AGOs). Crystal structures of archaeal and
bacterial homologues of AGOs have shown that the MID (middle) domain mediates
the interaction with the phosphorylated 5' end of the miRNA guide strand and
this interaction is thought to be independent of the identity of the 5'
nucleotide in these systems. However, analysis of the known sequences of
eukaryotic miRNAs and co-immunoprecipitation experiments indicate that there is
a clear bias for U or A at the 5' position. Here we report the crystal structure
of a MID domain from a eukaryotic AGO protein, human AGO2. The structure, in
complex with nucleoside monophosphates (AMP, CMP, GMP, and UMP) mimicking the 5'
end of miRNAs, shows that there are specific contacts made between the base of
UMP or AMP and a rigid loop in the MID domain. Notably, the structure of the
loop discriminates against CMP and GMP and dissociation constants calculated
from NMR titration experiments confirm these results, showing that AMP (0.26 mM)
and UMP (0.12 mM) bind with up to 30-fold higher affinity than either CMP (3.6
mM) or GMP (3.3 mM). This study provides structural evidence for
nucleotide-specific interactions in the MID domain of eukaryotic AGO proteins
and explains the observed preference for U or A at the 5' end of miRNAs.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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G.A.Mackie
(2012).
RNase E: at the interface of bacterial RNA processing and decay.
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Nat Rev Microbiol,
11,
45-57.
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H.M.Sasaki,
and
Y.Tomari
(2012).
The true core of RNA silencing revealed.
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Nat Struct Mol Biol,
19,
657-660.
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J.J.Ipsaro,
A.D.Haase,
S.R.Knott,
L.Joshua-Tor,
and
G.J.Hannon
(2012).
The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis.
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Nature,
491,
279-283.
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PDB codes:
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K.Nakanishi,
D.E.Weinberg,
D.P.Bartel,
and
D.J.Patel
(2012).
Structure of yeast Argonaute with guide RNA.
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Nature,
486,
368-374.
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PDB code:
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P.B.Kwak,
and
Y.Tomari
(2012).
The N domain of Argonaute drives duplex unwinding during RISC assembly.
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Nat Struct Mol Biol,
19,
145-151.
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B.Czech,
and
G.J.Hannon
(2011).
Small RNA sorting: matchmaking for Argonautes.
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Nat Rev Genet,
12,
19-31.
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C.Fellmann,
J.Zuber,
K.McJunkin,
K.Chang,
C.D.Malone,
R.A.Dickins,
Q.Xu,
M.O.Hengartner,
S.J.Elledge,
G.J.Hannon,
and
S.W.Lowe
(2011).
Functional identification of optimized RNAi triggers using a massively parallel sensor assay.
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Mol Cell,
41,
733-746.
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D.J.Obbard,
F.M.Jiggins,
N.J.Bradshaw,
and
T.J.Little
(2011).
Recent and recurrent selective sweeps of the antiviral RNAi gene Argonaute-2 in three species of Drosophila.
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Mol Biol Evol,
28,
1043-1056.
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E.Koscianska,
J.Starega-Roslan,
L.J.Sznajder,
M.Olejniczak,
P.Galka-Marciniak,
and
W.J.Krzyzosiak
(2011).
Northern blotting analysis of microRNAs, their precursors and RNA interference triggers.
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BMC Mol Biol,
12,
14.
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F.Frank,
M.R.Fabian,
J.Stepinski,
J.Jemielity,
E.Darzynkiewicz,
N.Sonenberg,
and
B.Nagar
(2011).
Structural analysis of 5'-mRNA-cap interactions with the human AGO2 MID domain.
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EMBO Rep,
12,
415-420.
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PDB codes:
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H.Zhu,
F.Hu,
R.Wang,
X.Zhou,
S.H.Sze,
L.W.Liou,
A.Barefoot,
M.Dickman,
and
X.Zhang
(2011).
Arabidopsis Argonaute10 specifically sequesters miR166/165 to regulate shoot apical meristem development.
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Cell,
145,
242-256.
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J.Starega-Roslan,
J.Krol,
E.Koscianska,
P.Kozlowski,
W.J.Szlachcic,
K.Sobczak,
and
W.J.Krzyzosiak
(2011).
Structural basis of microRNA length variety.
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Nucleic Acids Res,
39,
257-268.
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K.P.Jensen,
and
J.Covault
(2011).
Human miR-1271 is a miR-96 paralog with distinct non-conserved brain expression pattern.
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Nucleic Acids Res,
39,
701-711.
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S.Djuranovic,
A.Nahvi,
and
R.Green
(2011).
A parsimonious model for gene regulation by miRNAs.
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Science,
331,
550-553.
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S.L.Ameres,
J.H.Hung,
J.Xu,
Z.Weng,
and
P.D.Zamore
(2011).
Target RNA-directed tailing and trimming purifies the sorting of endo-siRNAs between the two Drosophila Argonaute proteins.
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RNA,
17,
54-63.
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A.Schaefer,
H.I.Im,
M.T.Venø,
C.D.Fowler,
A.Min,
A.Intrator,
J.Kjems,
P.J.Kenny,
D.O'Carroll,
and
P.Greengard
(2010).
Argonaute 2 in dopamine 2 receptor-expressing neurons regulates cocaine addiction.
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J Exp Med,
207,
1843-1851.
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C.R.Faehnle,
and
L.Joshua-Tor
(2010).
Argonaute MID domain takes centre stage.
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EMBO Rep,
11,
564-565.
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J.Krol,
I.Loedige,
and
W.Filipowicz
(2010).
The widespread regulation of microRNA biogenesis, function and decay.
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Nat Rev Genet,
11,
597-610.
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S.P.Walton,
M.Wu,
J.A.Gredell,
and
C.Chan
(2010).
Designing highly active siRNAs for therapeutic applications.
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FEBS J,
277,
4806-4813.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
