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Translation,hydrolase
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PDB id
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2ffl
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Gene Ontology (GO) functional annotation
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Biological process
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RNA processing
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3 terms
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Biochemical function
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nucleotide binding
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8 terms
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DOI no:
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Science
311:195-198
(2006)
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PubMed id:
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Structural basis for double-stranded RNA processing by Dicer.
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I.J.Macrae,
K.Zhou,
F.Li,
A.Repic,
A.N.Brooks,
W.Z.Cande,
P.D.Adams,
J.A.Doudna.
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ABSTRACT
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The specialized ribonuclease Dicer initiates RNA interference by cleaving
double-stranded RNA (dsRNA) substrates into small fragments about 25 nucleotides
in length. In the crystal structure of an intact Dicer enzyme, the PAZ domain, a
module that binds the end of dsRNA, is separated from the two catalytic
ribonuclease III (RNase III) domains by a flat, positively charged surface. The
65 angstrom distance between the PAZ and RNase III domains matches the length
spanned by 25 base pairs of RNA. Thus, Dicer itself is a molecular ruler that
recognizes dsRNA and cleaves a specified distance from the helical end.
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Selected figure(s)
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Figure 3.
Fig. 3. Structural features of the Dicer PAZ domain. (A)
Superposition of the C[  ]atoms of PAZ
domains from Giardia Dicer (orange) and human Argonaute1
(white). Amino acids forming the 3' overhang-binding pocket are
shown as sticks. (B) Electrostatic surface representation of the
PAZ domains of Giardia Dicer and Argonaute1 (hAGO1). Asterisks
denote 3' overhang-binding pockets. The RNA in Argonaute1 PAZ
structure is drawn as green sticks.
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Figure 4.
Fig. 4. A model for dsRNA processing by Dicer. Front and side
views of a surface representation of Giardia Dicer with modeled
dsRNA. Red and blue represent acidic and basic protein surface
charge, respectively. Electrostatic surface potentials do not
include contributions from bound metal ions. Putative catalytic
metal ions are shown as green spheres. White arrows point to
scissile phosphates. Asterisk denotes PAZ domain 3'
overhang-binding pocket.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2006,
311,
195-198)
copyright 2006.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
|
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| |
PubMed id
|
|
Reference
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|
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PDB codes:
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A.N.Khachane,
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RNA, 16,
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PDB code:
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J.P.Lu,
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| |
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PDB code:
|
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|
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|
|
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J.A.Snyder,
Y.B.Park,
Y.F.Li,
R.Sunkar,
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| |
RNA, 15,
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|
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and
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|
| |
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PDB codes:
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|
D.D.Rao,
J.S.Vorhies,
N.Senzer,
and
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| |
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| |
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|
| |
Nature, 461,
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|
PDB code:
|
|
|
|
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|
|
|
Y.Tagami,
H.Motose,
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A dominant mutation in DCL1 suppresses the hyl1 mutant phenotype by promoting the processing of miRNA.
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RNA, 15,
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Inhibition of dicing of guanosine-rich shRNAs by quadruplex-binding compounds.
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| |
Chembiochem, 9,
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and
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(2008).
Antigenic variation in Giardia lamblia is regulated by RNA interference.
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| |
Nature, 456,
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(2008).
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| |
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|
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|
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J.F.Kirsch,
and
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(2008).
Autoinhibition of human dicer by its internal helicase domain.
|
| |
J Mol Biol, 380,
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|
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|
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R.D.Morin,
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J.Mattsson,
and
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(2008).
Conifers have a unique small RNA silencing signature.
|
| |
RNA, 14,
1508-1515.
|
|
|
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PLoS ONE, 3,
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Proc Natl Acad Sci U S A, 105,
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PDB codes:
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|
d.o. .H.Lim,
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Biochem Biophys Res Commun, 371,
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A.V.Vlassov,
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shRNAs targeting hepatitis C: effects of sequence and structural features, and comparision with siRNA.
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Oligonucleotides, 17,
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Nat Rev Mol Cell Biol, 8,
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FEBS Lett, 581,
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An unusual case of pseudo-merohedral twinning in orthorhombic crystals of Dicer.
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Acta Crystallogr D Biol Crystallogr, 63,
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|
PDB code:
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I.J.MacRae,
and
J.A.Doudna
(2007).
Ribonuclease revisited: structural insights into ribonuclease III family enzymes.
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Curr Opin Struct Biol, 17,
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Nat Struct Mol Biol, 14,
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Curr Opin Struct Biol, 17,
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J.Jiang,
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and
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(2007).
Selenium derivatization of nucleic acids for crystallography.
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Nucleic Acids Res, 35,
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PDB codes:
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|
M.D.Woodhams,
P.F.Stadler,
D.Penny,
and
L.J.Collins
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RNase MRP and the RNA processing cascade in the eukaryotic ancestor.
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BMC Evol Biol, 7,
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M.Meissner,
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W.J.Sullivan
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Molecular tools for analysis of gene function in parasitic microorganisms.
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Appl Microbiol Biotechnol, 75,
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M.Thomas,
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Non-viral siRNA delivery to the lung.
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Adv Drug Deliv Rev, 59,
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R.Cottam,
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Re-mapping Robert Rosen's (M,R)-systems.
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Chem Biodivers, 4,
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S.Hur,
and
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(2007).
How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA.
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| |
Mol Cell, 26,
189-203.
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|
PDB codes:
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|
S.U.Colmenares,
S.M.Buker,
M.Buhler,
M.Dlakić,
and
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(2007).
Coupling of double-stranded RNA synthesis and siRNA generation in fission yeast RNAi.
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Mol Cell, 27,
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S.Y.Sohn,
W.J.Bae,
J.J.Kim,
K.H.Yeom,
V.N.Kim,
and
Y.Cho
(2007).
Crystal structure of human DGCR8 core.
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| |
Nat Struct Mol Biol, 14,
847-853.
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|
PDB code:
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|
|
T.Federici,
and
N.M.Boulis
(2007).
Ribonucleic acid interference for neurological disorders: candidate diseases, potential targets, and current approaches.
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Neurosurgery, 60,
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T.Katoh,
and
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(2007).
Specific residues at every third position of siRNA shape its efficient RNAi activity.
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Nucleic Acids Res, 35,
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W.Ritchie,
M.Legendre,
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(2007).
RNA stem-loops: to be or not to be cleaved by RNAse III.
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RNA, 13,
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X.S.Chen,
T.S.Rozhdestvensky,
L.J.Collins,
J.Schmitz,
and
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(2007).
Combined experimental and computational approach to identify non-protein-coding RNAs in the deep-branching eukaryote Giardia intestinalis.
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Nucleic Acids Res, 35,
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A.A.Seyhan,
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RNA interference from multimeric shRNAs generated by rolling circle transcription.
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Oligonucleotides, 16,
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Dicer measures up.
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Nat Struct Mol Biol, 13,
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A.V.Pertzev,
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Characterization of RNA sequence determinants and antideterminants of processing reactivity for a minimal substrate of Escherichia coli ribonuclease III.
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Nucleic Acids Res, 34,
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B.P.Davies,
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A homogenous assay for micro RNA maturation.
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Angew Chem Int Ed Engl, 45,
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Is RNA interference involved in intrinsic antiviral immunity in mammals?
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Nat Immunol, 7,
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Artificial control of gene expression in mammalian cells by modulating RNA interference through aptamer-small molecule interaction.
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RNA, 12,
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D.J.Patel,
J.B.Ma,
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Structural biology of RNA silencing and its functional implications.
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Cold Spring Harb Symp Quant Biol, 71,
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Substrate selectivity of exportin 5 and Dicer in the biogenesis of microRNAs.
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Cold Spring Harb Symp Quant Biol, 71,
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The expanding universe of noncoding RNAs.
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Cold Spring Harb Symp Quant Biol, 71,
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On the origin and functions of RNA-mediated silencing: from protists to man.
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An unusual Dicer-like1 protein fuels the RNA interference pathway in Trypanosoma brucei.
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RNA, 12,
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Structure of Dicer and mechanistic implications for RNAi.
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Cold Spring Harb Symp Quant Biol, 71,
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Short interfering RNA strand selection is independent of dsRNA processing polarity during RNAi in Drosophila.
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Curr Biol, 16,
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Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex.
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Cell, 125,
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J Biomed Biotechnol, 2006,
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J Cell Biochem, 99,
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Structural basis for non-catalytic and catalytic activities of ribonuclease III.
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Acta Crystallogr D Biol Crystallogr, 62,
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Y.Lee,
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H.Jin,
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Drosha in primary microRNA processing.
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Cold Spring Harb Symp Quant Biol, 71,
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A potential protein-RNA recognition event along the RISC-loading pathway from the structure of A. aeolicus Argonaute with externally bound siRNA.
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| |
Structure, 14,
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|
|
PDB codes:
|
|
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|
|
|
|
|
Y.Zeng
(2006).
Principles of micro-RNA production and maturation.
|
| |
Oncogene, 25,
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|
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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.
|
|
Links
