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Gene regulation
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PDB id
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1xtk
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* Residue conservation analysis
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Enzyme class:
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E.C.3.6.4.13
- Rna helicase.
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Reaction:
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ATP + H2O = ADP + phosphate
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ATP
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+
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H(2)O
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=
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ADP
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+
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phosphate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Cellular component
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nucleus
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6 terms
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Biological process
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transport
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9 terms
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Biochemical function
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nucleotide binding
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14 terms
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DOI no:
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Proc Natl Acad Sci U S A
101:17628-17633
(2004)
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PubMed id:
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Crystal structure of the human ATP-dependent splicing and export factor UAP56.
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H.Shi,
O.Cordin,
C.M.Minder,
P.Linder,
R.M.Xu.
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ABSTRACT
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Pre-mRNA splicing requires the function of a number of RNA-dependent
ATPases/helicases, yet no three-dimensional structure of any spliceosomal
ATPases/helicases is known. The highly conserved DECD-box protein UAP56/Sub2 is
an essential splicing factor that is also important for mRNA export. The
expected ATPase/helicase activity appears to be essential for the UAP56/Sub2
functions. Here, we show that purified human UAP56 is an active RNA-dependent
ATPase, and we also report the crystal structures of UAP56 alone and in complex
with ADP, as well as a DECD to DEAD mutant. The structures reveal a unique
spatial arrangement of the two conserved helicase domains, and ADP-binding
induces significant conformational changes of key residues in the ATP-binding
pocket. Our structural analyses suggest a specific protein-RNA displacement
model of UAP56/Sub2. The detailed structural information provides important
mechanistic insights into the splicing function of UAP56/Sub2. The structures
also will be useful for the analysis of other spliceosomal DExD-box
ATPases/helicases.
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Selected figure(s)
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Figure 2.
Fig. 2. Overall structure. The structure of UAP56  N is
shown as a ribbon model (A) and in a surface representation (B),
viewed from a similar direction. (A) Cyan, N-terminal domain;
brown, C-terminal domain; green, interdomain linker. Locations
of conserved helicase sequence motifs are labeled. (B) Blue,
positively charged electrostatic potential; white, neutral
electrostatic potential; red, negatively charged electrostatic
potential. A large ATP-binding cleft is formed between the N-
and C-terminal helicase domains.
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Figure 4.
Fig. 4. Domain organizations. (A) The UAP56 structure
(cyan) is superimposed with the structures of yeast eIF4A (red;
PDB ID code 1FUU [PDB]
) and mjDEAD (yellow; PDB ID code 1HV8 [PDB]
). The N-terminal domains were aligned. The dashed magenta line
indicates the axis around which a rotation of  50°
will superimpose the C-terminal domain of UAP56 with that of
mjDEAD. (B) Superposition of UAP56 with hepatitis C virus
helicase (PDB ID code 1A1V [PDB]
) (helicase domains shown in green; extra domain shown in
magenta and beige), viewed from a perpendicular direction (from
left to right) with respect to that in A. The magenta dashed arc
indicates a rotation of 71° between the two
C-terminal domains. The single-stranded DNA oligo bound to the
viral helicase is shown in a stick model.
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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
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Reference
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J.Strohmeier,
I.Hertel,
U.Diederichsen,
M.G.Rudolph,
and
D.Klostermeier
(2011).
Changing nucleotide specificity of the DEAD-box helicase Hera abrogates communication between the Q-motif and the P-loop.
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| |
Biol Chem, 392,
357-369.
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PDB codes:
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C.L.Brinkmeyer-Langford,
W.J.Murphy,
C.P.Childers,
and
L.C.Skow
(2010).
A conserved segmental duplication within ELA.
|
| |
Anim Genet, 41,
186-195.
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R.Tuteja,
and
J.Mehta
(2010).
A genomic glance at the components of the mRNA export machinery in Plasmodium falciparum.
|
| |
Commun Integr Biol, 3,
318-326.
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|
|
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|
|
T.C.Chang,
and
W.S.Liu
(2010).
The molecular evolution of PL10 homologs.
|
| |
BMC Evol Biol, 10,
127.
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|
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|
|
D.Klostermeier,
and
M.G.Rudolph
(2009).
A novel dimerization motif in the C-terminal domain of the Thermus thermophilus DEAD box helicase Hera confers substantial flexibility.
|
| |
Nucleic Acids Res, 37,
421-430.
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PDB codes:
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F.Tritschler,
J.E.Braun,
A.Eulalio,
V.Truffault,
E.Izaurralde,
and
O.Weichenrieder
(2009).
Structural basis for the mutually exclusive anchoring of P body components EDC3 and Tral to the DEAD box protein DDX6/Me31B.
|
| |
Mol Cell, 33,
661-668.
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|
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PDB codes:
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H.von Moeller,
C.Basquin,
and
E.Conti
(2009).
The mRNA export protein DBP5 binds RNA and the cytoplasmic nucleoporin NUP214 in a mutually exclusive manner.
|
| |
Nat Struct Mol Biol, 16,
247-254.
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PDB codes:
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J.Napetschnig,
S.A.Kassube,
E.W.Debler,
R.W.Wong,
G.Blobel,
and
A.Hoelz
(2009).
Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19.
|
| |
Proc Natl Acad Sci U S A, 106,
3089-3094.
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PDB codes:
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L.Zhang,
T.Xu,
C.Maeder,
L.O.Bud,
J.Shanks,
J.Nix,
C.Guthrie,
J.A.Pleiss,
and
R.Zhao
(2009).
Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2.
|
| |
Nat Struct Mol Biol, 16,
731-739.
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PDB code:
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M.G.Rudolph,
J.G.Wittmann,
and
D.Klostermeier
(2009).
Crystallization and preliminary characterization of the Thermus thermophilus RNA helicase Hera C-terminal domain.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun, 65,
248-252.
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|
|
N.T.Uyen,
S.Y.Park,
J.W.Choi,
H.J.Lee,
K.Nishi,
and
J.S.Kim
(2009).
The fragment structure of a putative HsdR subunit of a type I restriction enzyme from Vibrio vulnificus YJ016: implications for DNA restriction and translocation activity.
|
| |
Nucleic Acids Res, 37,
6960-6969.
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PDB code:
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S.Chimnaronk,
T.Suzuki,
T.Manita,
Y.Ikeuchi,
M.Yao,
T.Suzuki,
and
I.Tanaka
(2009).
RNA helicase module in an acetyltransferase that modifies a specific tRNA anticodon.
|
| |
EMBO J, 28,
1362-1373.
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|
PDB code:
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S.H.Ling,
Z.Cheng,
and
H.Song
(2009).
Structural aspects of RNA helicases in eukaryotic mRNA decay.
|
| |
Biosci Rep, 29,
339-349.
|
|
|
|
|
|
|
A.Henn,
W.Cao,
D.D.Hackney,
and
E.M.De La Cruz
(2008).
The ATPase cycle mechanism of the DEAD-box rRNA helicase, DbpA.
|
| |
J Mol Biol, 377,
193-205.
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|
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|
|
A.Obarska-Kosinska,
J.E.Taylor,
P.Callow,
J.Orlowski,
J.M.Bujnicki,
and
G.G.Kneale
(2008).
HsdR subunit of the type I restriction-modification enzyme EcoR124I: biophysical characterisation and structural modelling.
|
| |
J Mol Biol, 376,
438-452.
|
|
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|
|
B.Theissen,
A.R.Karow,
J.Köhler,
A.Gubaev,
and
D.Klostermeier
(2008).
Cooperative binding of ATP and RNA induces a closed conformation in a DEAD box RNA helicase.
|
| |
Proc Natl Acad Sci U S A, 105,
548-553.
|
|
|
|
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|
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H.Le Hir,
and
G.R.Andersen
(2008).
Structural insights into the exon junction complex.
|
| |
Curr Opin Struct Biol, 18,
112-119.
|
|
|
|
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|
|
H.Shen,
X.Zheng,
J.Shen,
L.Zhang,
R.Zhao,
and
M.R.Green
(2008).
Distinct activities of the DExD/H-box splicing factor hUAP56 facilitate stepwise assembly of the spliceosome.
|
| |
Genes Dev, 22,
1796-1803.
|
|
|
|
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|
|
I.Taniguchi,
and
M.Ohno
(2008).
ATP-dependent recruitment of export factor Aly/REF onto intronless mRNAs by RNA helicase UAP56.
|
| |
Mol Cell Biol, 28,
601-608.
|
|
|
|
|
|
|
R.Luna,
H.Gaillard,
C.González-Aguilera,
and
A.Aguilera
(2008).
Biogenesis of mRNPs: integrating different processes in the eukaryotic nucleus.
|
| |
Chromosoma, 117,
319-331.
|
|
|
|
|
|
|
A.Cook,
F.Bono,
M.Jinek,
and
E.Conti
(2007).
Structural biology of nucleocytoplasmic transport.
|
| |
Annu Rev Biochem, 76,
647-671.
|
|
|
|
|
|
|
A.R.Karow,
B.Theissen,
and
D.Klostermeier
(2007).
Authentic interdomain communication in an RNA helicase reconstituted by expressed protein ligation of two helicase domains.
|
| |
FEBS J, 274,
463-473.
|
|
|
|
|
|
|
E.Jankowsky,
and
M.E.Fairman
(2007).
RNA helicases--one fold for many functions.
|
| |
Curr Opin Struct Biol, 17,
316-324.
|
|
|
|
|
|
|
R.Franca,
A.Belfiore,
S.Spadari,
and
G.Maga
(2007).
Human DEAD-box ATPase DDX3 shows a relaxed nucleoside substrate specificity.
|
| |
Proteins, 67,
1128-1137.
|
|
|
|
|
|
|
D.Keramisanou,
N.Biris,
I.Gelis,
G.Sianidis,
S.Karamanou,
A.Economou,
and
C.G.Kalodimos
(2006).
Disorder-order folding transitions underlie catalysis in the helicase motor of SecA.
|
| |
Nat Struct Mol Biol, 13,
594-602.
|
|
|
|
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|
|
H.Uhlmann-Schiffler,
C.Jalal,
and
H.Stahl
(2006).
Ddx42p--a human DEAD box protein with RNA chaperone activities.
|
| |
Nucleic Acids Res, 34,
10-22.
|
|
|
|
|
|
|
J.M.Caruthers,
Y.Hu,
and
D.B.McKay
(2006).
Structure of the second domain of the Bacillus subtilis DEAD-box RNA helicase YxiN.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun, 62,
1191-1195.
|
|
|
PDB code:
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|
|
M.E.Bordeleau,
A.Mori,
M.Oberer,
L.Lindqvist,
L.S.Chard,
T.Higa,
G.J.Belsham,
G.Wagner,
J.Tanaka,
and
J.Pelletier
(2006).
Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A.
|
| |
Nat Chem Biol, 2,
213-220.
|
|
|
|
|
|
|
N.Tanaka,
and
B.Schwer
(2006).
Mutations in PRP43 that uncouple RNA-dependent NTPase activity and pre-mRNA splicing function.
|
| |
Biochemistry, 45,
6510-6521.
|
|
|
|
|
|
|
O.T.Kim,
K.Yura,
and
N.Go
(2006).
Amino acid residue doublet propensity in the protein-RNA interface and its application to RNA interface prediction.
|
| |
Nucleic Acids Res, 34,
6450-6460.
|
|
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|
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|
|
P.Huertas,
M.L.García-Rubio,
R.E.Wellinger,
R.Luna,
and
A.Aguilera
(2006).
An hpr1 point mutation that impairs transcription and mRNP biogenesis without increasing recombination.
|
| |
Mol Cell Biol, 26,
7451-7465.
|
|
|
|
|
|
|
P.Linder
(2006).
Dead-box proteins: a family affair--active and passive players in RNP-remodeling.
|
| |
Nucleic Acids Res, 34,
4168-4180.
|
|
|
|
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|
|
S.Jimeno,
R.Luna,
M.García-Rubio,
and
A.Aguilera
(2006).
Tho1, a novel hnRNP, and Sub2 provide alternative pathways for mRNP biogenesis in yeast THO mutants.
|
| |
Mol Cell Biol, 26,
4387-4398.
|
|
|
|
|
|
|
S.Wang,
Y.Hu,
M.T.Overgaard,
F.V.Karginov,
O.C.Uhlenbeck,
and
D.B.McKay
(2006).
The domain of the Bacillus subtilis DEAD-box helicase YxiN that is responsible for specific binding of 23S rRNA has an RNA recognition motif fold.
|
| |
RNA, 12,
959-967.
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|
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PDB code:
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T.Sengoku,
O.Nureki,
A.Nakamura,
S.Kobayashi,
and
S.Yokoyama
(2006).
Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa.
|
| |
Cell, 125,
287-300.
|
|
|
PDB code:
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A.Aguilera
(2005).
Cotranscriptional mRNP assembly: from the DNA to the nuclear pore.
|
| |
Curr Opin Cell Biol, 17,
242-250.
|
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|
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M.Oberer,
A.Marintchev,
and
G.Wagner
(2005).
Structural basis for the enhancement of eIF4A helicase activity by eIF4G.
|
| |
Genes Dev, 19,
2212-2223.
|
|
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|
|
Z.Cheng,
J.Coller,
R.Parker,
and
H.Song
(2005).
Crystal structure and functional analysis of DEAD-box protein Dhh1p.
|
| |
RNA, 11,
1258-1270.
|
|
|
PDB code:
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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
