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PDBsum entry 3d2s
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Metal binding protein/RNA
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PDB id
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3d2s
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Contents |
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* Residue conservation analysis
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PDB id:
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Metal binding protein/RNA
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Title:
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Crystal structure of mbnl1 tandem zinc finger 3 and 4 domain in complex with cgcugu RNA
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Structure:
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5'-r( Cp Gp Cp Up Gp U)-3'. Chain: e, f, g, h. Engineered: yes. Muscleblind-like protein 1. Chain: a, b, c, d. Fragment: tandem zinc finger 3 and 4 domains (unp residues 178-246). Synonym: triplet-expansion RNA-binding protein. Engineered: yes
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Source:
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Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Other_details: chemically synthesized RNA oligonucleotide. Homo sapiens. Human. Organism_taxid: 9606. Gene: mbnl1, exp, kiaa0428, mbnl. Expressed in: escherichia coli.
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Resolution:
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1.70Å
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R-factor:
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0.226
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R-free:
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0.260
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Authors:
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M.Teplova,D.J.Patel
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Key ref:
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M.Teplova
and
D.J.Patel
(2008).
Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1.
Nat Struct Biol,
15,
1343-1351.
PubMed id:
DOI:
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Date:
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08-May-08
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Release date:
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02-Dec-08
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PROCHECK
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Headers
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References
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Q9NR56
(MBNL1_HUMAN) -
Muscleblind-like protein 1 from Homo sapiens
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Seq:
Struc:
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388 a.a.
67 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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C-G-C-U-G-U
6 bases
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C-G-C-U-G
5 bases
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C-G-C-U-G-U
6 bases
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C-G-C-U-G
5 bases
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DOI no:
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Nat Struct Biol
15:1343-1351
(2008)
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PubMed id:
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Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1.
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M.Teplova,
D.J.Patel.
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ABSTRACT
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Muscleblind-like (MBNL) proteins, regulators of developmentally programmed
alternative splicing, harbor tandem CCCH zinc-finger (ZnF) domains that target
pre-mRNAs containing YGCU(U/G)Y sequence elements (where Y is a pyrimidine). In
myotonic dystrophy, reduced levels of MBNL proteins lead to aberrant alternative
splicing of a subset of pre-mRNAs. The crystal structure of MBNL1 ZnF3/4 bound
to r(CGCUGU) establishes that both ZnF3 and ZnF4 target GC steps, with
site-specific recognition mediated by a network of hydrogen bonds formed
primarily with main chain groups of the protein. The relative alignment of ZnF3
and ZnF4 domains is dictated by the topology of the interdomain linker, with a
resulting antiparallel orientation of bound GC elements, supportive of a
chain-reversal loop trajectory for MBNL1-bound pre-mRNA targets. We anticipate
that MBNL1-mediated targeting of looped RNA segments proximal to splice-site
junctions could contribute to pre-mRNA alternative-splicing regulation.
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Selected figure(s)
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Figure 3.
(a) Ribbon and stick representation of the complex containing
one MBNL1 ZnF3/4 domain (molecule A) and three RNAs bound by
ZnF3 and ZnF4. The ZnF3/4 molecule A is colored light blue.
Cysteine and histidine residues coordinating zinc atoms are
shown in ball-and-stick representation. The two symmetry-related
RNA strands are colored pink and the third RNA strand is colored
light orange. The G5 and 5'-C1 nucleotides originating from two
RNA strands are bound to ZnF3, whereas the G2-C3-U4 segment of
the third strand is bound to the ZnF4 motif. (b) An
electrostatic view of the molecule A complex generated using the
GRASP and PyMol programs. Basic and acidic regions appear in
blue and red, with the intensity of the color proportional to
the local potential. (c) View of the protein-RNA interface
highlighting intermolecular contacts between G2-C3-U4 segment
and MBNL1 ZnF4. Stacking interactions of G2 and C3 bases with
arginine and aromatic residues, as well as hydrogen-bonding
contacts involving G2, C3 and U4, are highlighted. (d)
Electrostatic surface representation of the protein-RNA
interface in the same view as in c.
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Figure 4.
(a) Hydrogen-bonding of the N^2 and N^1 of G5 with the side
chain thiols of zinc-bound Cys185 and Cys200 and the O^6 of G5
with the backbone amide of Arg201 of the molecule A ZnF3 motif.
G5 stacks with Arg195 of the ZnF3 motif.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2008,
15,
1343-1351)
copyright 2008.
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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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S.Chen,
Y.Xu,
K.Zhang,
X.Wang,
J.Sun,
G.Gao,
and
Y.Liu
(2012).
Structure of N-terminal domain of ZAP indicates how a zinc-finger protein recognizes complex RNA.
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Nat Struct Mol Biol,
19,
430-435.
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PDB code:
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E.S.Goers,
J.Purcell,
R.B.Voelker,
D.P.Gates,
and
J.A.Berglund
(2010).
MBNL1 binds GC motifs embedded in pyrimidines to regulate alternative splicing.
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Nucleic Acids Res,
38,
2467-2484.
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H.Du,
M.S.Cline,
R.J.Osborne,
D.L.Tuttle,
T.A.Clark,
J.P.Donohue,
M.P.Hall,
L.Shiue,
M.S.Swanson,
C.A.Thornton,
and
M.Ares
(2010).
Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy.
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Nat Struct Mol Biol,
17,
187-193.
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J.Kralovicova,
and
I.Vorechovsky
(2010).
Allele-specific recognition of the 3' splice site of INS intron 1.
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Hum Genet,
128,
383-400.
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J.M.Fernandez-Costa,
and
R.Artero
(2010).
A conserved motif controls nuclear localization of Drosophila Muscleblind.
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Mol Cells,
30,
65-70.
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M.B.Warf,
and
J.A.Berglund
(2010).
Role of RNA structure in regulating pre-mRNA splicing.
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Trends Biochem Sci,
35,
169-178.
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Q.Yang,
G.M.Gilmartin,
and
S.Doublié
(2010).
Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing.
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Proc Natl Acad Sci U S A,
107,
10062-10067.
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PDB codes:
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S.Eustermann,
C.Brockmann,
P.V.Mehrotra,
J.C.Yang,
D.Loakes,
S.C.West,
I.Ahel,
and
D.Neuhaus
(2010).
Solution structures of the two PBZ domains from human APLF and their interaction with poly(ADP-ribose).
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Nat Struct Mol Biol,
17,
241-243.
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PDB codes:
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A.Kiliszek,
R.Kierzek,
W.J.Krzyzosiak,
and
W.Rypniewski
(2009).
Structural insights into CUG repeats containing the 'stretched U-U wobble': implications for myotonic dystrophy.
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Nucleic Acids Res,
37,
4149-4156.
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PDB codes:
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A.Pushechnikov,
M.M.Lee,
J.L.Childs-Disney,
K.Sobczak,
J.M.French,
C.A.Thornton,
and
M.D.Disney
(2009).
Rational design of ligands targeting triplet repeating transcripts that cause RNA dominant disease: application to myotonic muscular dystrophy type 1 and spinocerebellar ataxia type 3.
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J Am Chem Soc,
131,
9767-9779.
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M.B.Warf,
J.V.Diegel,
P.H.von Hippel,
and
J.A.Berglund
(2009).
The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing.
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Proc Natl Acad Sci U S A,
106,
9203-9208.
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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
code is
shown on the right.
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Links
