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PDBsum entry 2p8r
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* Residue conservation analysis
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DOI no:
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Protein Sci
16:1024-1031
(2007)
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PubMed id:
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Crystal structure of the C-terminal domain of splicing factor Prp8 carrying retinitis pigmentosa mutants.
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L.Zhang,
J.Shen,
M.T.Guarnieri,
A.Heroux,
K.Yang,
R.Zhao.
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ABSTRACT
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Prp8 is a critical pre-mRNA splicing factor. Prp8 is proposed to help form and
stabilize the spliceosome catalytic core and to be an important regulator of
spliceosome activation. Mutations in human Prp8 (hPrp8) cause a severe form of
the genetic disorder retinitis pigmentosa, RP13. Understanding the molecular
mechanism of Prp8's function in pre-mRNA splicing and RP13 has been hindered by
its large size (over 2000 amino acids) and remarkably low-sequence similarity
with other proteins. Here we present the crystal structure of the C-terminal
domain (the last 273 residues) of Caenorhabditis elegans Prp8 (cPrp8). The core
of the C-terminal domain is an alpha/beta structure that forms the MPN (Mpr1,
Pad1 N-terminal) fold but without Zn(2+) coordination. We propose that the
C-terminal domain is a protein interaction domain instead of a Zn(2+)-dependent
metalloenzyme as proposed for some MPN proteins. Mapping of RP13 mutants on the
Prp8 structure suggests that these residues constitute a binding surface between
Prp8 and other partner(s), and the disruption of this interaction provides a
plausible molecular mechanism for RP13.
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Selected figure(s)
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Figure 4.
Figure 4. RP13 mutations. (A, left) Residues corresponding to the human RP13 mutations (ball and stick models) are located on the
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The above figure is
reprinted
by permission from the Protein Society:
Protein Sci
(2007,
16,
1024-1031)
copyright 2007.
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Figure was
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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W.P.Galej,
C.Oubridge,
A.J.Newman,
and
K.Nagai
(2013).
Crystal structure of Prp8 reveals active site cavity of the spliceosome.
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Nature,
493,
638-643.
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PDB codes:
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S.Valadkhan,
and
Y.Jaladat
(2010).
The spliceosomal proteome: at the heart of the largest cellular ribonucleoprotein machine.
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Proteomics,
10,
4128-4141.
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C.Maeder,
A.K.Kutach,
and
C.Guthrie
(2009).
ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8.
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Nat Struct Mol Biol,
16,
42-48.
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C.Netter,
G.Weber,
H.Benecke,
and
M.C.Wahl
(2009).
Functional stabilization of an RNA recognition motif by a noncanonical N-terminal expansion.
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RNA,
15,
1305-1313.
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PDB code:
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D.A.Brow
(2009).
Eye on RNA unwinding.
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Nat Struct Mol Biol,
16,
7-8.
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F.E.Reyes-Turcu,
and
K.D.Wilkinson
(2009).
Polyubiquitin binding and disassembly by deubiquitinating enzymes.
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Chem Rev,
109,
1495-1508.
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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.
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Nat Struct Mol Biol,
16,
731-739.
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PDB code:
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M.C.Wahl,
C.L.Will,
and
R.Lührmann
(2009).
The spliceosome: design principles of a dynamic RNP machine.
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Cell,
136,
701-718.
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C.Maeder,
and
C.Guthrie
(2008).
Modifications target spliceosome dynamics.
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Nat Struct Mol Biol,
15,
426-428.
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J.Abelson
(2008).
Is the spliceosome a ribonucleoprotein enzyme?
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Nat Struct Mol Biol,
15,
1235-1237.
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J.Sperling,
M.Azubel,
and
R.Sperling
(2008).
Structure and function of the Pre-mRNA splicing machine.
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Structure,
16,
1605-1615.
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K.Yang,
L.Zhang,
T.Xu,
A.Heroux,
and
R.Zhao
(2008).
Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins.
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Proc Natl Acad Sci U S A,
105,
13817-13822.
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PDB code:
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L.Ivings,
K.V.Towns,
M.A.Matin,
C.Taylor,
F.Ponchel,
R.J.Grainger,
R.S.Ramesar,
D.A.Mackey,
and
C.F.Inglehearn
(2008).
Evaluation of splicing efficiency in lymphoblastoid cell lines from patients with splicing-factor retinitis pigmentosa.
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Mol Vis,
14,
2357-2366.
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M.Hebeisen,
J.Drysdale,
and
R.Roy
(2008).
Suppressors of the cdc-25.1(gf)-associated intestinal hyperplasia reveal important maternal roles for prp-8 and a subset of splicing factors in C. elegans.
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RNA,
14,
2618-2633.
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M.S.Jurica
(2008).
Detailed close-ups and the big picture of spliceosomes.
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Curr Opin Struct Biol,
18,
315-320.
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P.Bellare,
E.C.Small,
X.Huang,
J.A.Wohlschlegel,
J.P.Staley,
and
E.J.Sontheimer
(2008).
A role for ubiquitin in the spliceosome assembly pathway.
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Nat Struct Mol Biol,
15,
444-451.
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V.Pena,
A.Rozov,
P.Fabrizio,
R.Lührmann,
and
M.C.Wahl
(2008).
Structure and function of an RNase H domain at the heart of the spliceosome.
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EMBO J,
27,
2929-2940.
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PDB codes:
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Y.Sato,
A.Yoshikawa,
A.Yamagata,
H.Mimura,
M.Yamashita,
K.Ookata,
O.Nureki,
K.Iwai,
M.Komada,
and
S.Fukai
(2008).
Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains.
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Nature,
455,
358-362.
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PDB codes:
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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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