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PDBsum entry 1xk5
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Transport protein
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PDB id
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1xk5
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Contents |
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* Residue conservation analysis
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DOI no:
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EMBO J
24:2235-2243
(2005)
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PubMed id:
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Structural basis for m3G-cap-mediated nuclear import of spliceosomal UsnRNPs by snurportin1.
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A.Strasser,
A.Dickmanns,
R.Lührmann,
R.Ficner.
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ABSTRACT
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In higher eukaryotes the biogenesis of spliceosomal UsnRNPs involves a
nucleocytoplasmic shuttling cycle. After the m7G-cap-dependent export of the
snRNAs U1, U2, U4 and U5 to the cytoplasm, each of these snRNAs associates with
seven Sm proteins. Subsequently, the m7G-cap is hypermethylated to the
2,2,7-trimethylguanosine (m3G)-cap. The import adaptor snurportin1 recognises
the m3G-cap and facilitates the nuclear import of the UsnRNPs by binding to
importin-beta. Here we report the crystal structure of the m3G-cap-binding
domain of snurportin1 with bound m3GpppG at 2.4 A resolution, revealing a
structural similarity to the mRNA-guanyly-transferase. Snurportin1 binds both
the hypermethylated cap and the first nucleotide of the RNA in a stacked
conformation. This binding mode differs significantly from that of the
m7G-cap-binding proteins Cap-binding protein 20 (CBP20), eukaryotic initiation
factor 4E (eIF4E) and viral protein 39 (VP39). The specificity of the m3G-cap
recognition by snurportin1 was evaluated by fluorescence spectroscopy,
demonstrating the importance of a highly solvent exposed tryptophan for the
discrimination of m7G-capped RNAs. The critical role of this tryptophan and as
well of a tryptophan continuing the RNA base stack was confirmed by nuclear
import assays and cap-binding activity tests using several snurportin1 mutants.
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Selected figure(s)
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Figure 3.
Figure 3 Comparison of cap-binding pockets. m7G-cap-binding
pockets of CBP20, eIF4E and the viral nucleoside
2'-O-methyltransferase (VP39) are presented in comparison to the
m[3]G-cap-binding pocket of snurportin1. Side chains of residues
interacting with the caps are depicted in ball-and-stick mode.
Atoms of the caps and the interacting side chains are coloured
as described in Figure 1, with the exception of carbon atoms of
the dinucleotide, which are shown in orange. In all presented
cases, the residues stacking the bases and those forming
hydrogen bonds with the cap bases are depicted. Hydrogen bonds
are shown as dashed grey lines.
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Figure 5.
Figure 5 Structural similarity of snurportin1 with bound
m[3]GpppG to the mRNA-guanylyltransferase with bound GTP. (A)
Superimposed protein structures presented as ribbon diagrams and
the bound nucleotides in ball-and-stick representation. Human
snurportin1 -m[3]GpppG complex (coloured red) and the
mRNA-guanylyltransferase -GTP complex (coloured grey) of the
Paramecium bursaria chlorella virus 1 (PDB accession code 1CKM)
share an amino-acid sequence identity of 8.3% for the
structurally homologous regions. (B) Close-up view of the
nucleotide-binding pockets. In the mRNA-guanylyltransferase, the
bound GTP protrudes much deeper into the cleft between the  -sheets.
(C) Structure-based sequence alignment of human snurportin1 and
human mRNA-guanylyltransferase reveals a sequence identity of
12.7%.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2005,
24,
2235-2243)
copyright 2005.
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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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K.Ruszczyńska-Bartnik,
M.Maciejczyk,
and
R.Stolarski
(2011).
Dynamical insight into Caenorhabditis elegans eIF4E recognition specificity for mono-and trimethylated structures of mRNA 5' cap.
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J Mol Model,
17,
727-737.
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E.Kühn-Hölsken,
C.Lenz,
A.Dickmanns,
H.H.Hsiao,
F.M.Richter,
B.Kastner,
R.Ficner,
and
H.Urlaub
(2010).
Mapping the binding site of snurportin 1 on native U1 snRNP by cross-linking and mass spectrometry.
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Nucleic Acids Res,
38,
5581-5593.
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E.W.Debler,
G.Blobel,
and
A.Hoelz
(2009).
Nuclear transport comes full circle.
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Nat Struct Mol Biol,
16,
457-459.
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K.S.McKeegan,
C.M.Debieux,
and
N.J.Watkins
(2009).
Evidence that the AAA+ proteins TIP48 and TIP49 bridge interactions between 15.5K and the related NOP56 and NOP58 proteins during box C/D snoRNP biogenesis.
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Mol Cell Biol,
29,
4971-4981.
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M.Goette,
and
H.Grubmüller
(2009).
Accuracy and convergence of free energy differences calculated from nonequilibrium switching processes.
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J Comput Chem,
30,
447-456.
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M.Goette,
M.C.Stumpe,
R.Ficner,
and
H.Grubmüller
(2009).
Molecular determinants of snurportin 1 ligand affinity and structural response upon binding.
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Biophys J,
97,
581-589.
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M.Wu,
P.Nilsson,
N.Henriksson,
A.Niedzwiecka,
M.K.Lim,
Z.Cheng,
K.Kokkoris,
A.Virtanen,
and
H.Song
(2009).
Structural basis of m(7)GpppG binding to poly(A)-specific ribonuclease.
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Structure,
17,
276-286.
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PDB code:
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P.M.Moreno,
M.Wenska,
K.E.Lundin,
O.Wrange,
R.Strömberg,
and
C.I.Smith
(2009).
A synthetic snRNA m3G-CAP enhances nuclear delivery of exogenous proteins and nucleic acids.
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Nucleic Acids Res,
37,
1925-1935.
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T.Monecke,
A.Dickmanns,
A.Strasser,
and
R.Ficner
(2009).
Structure analysis of the conserved methyltransferase domain of human trimethylguanosine synthase TGS1.
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Acta Crystallogr D Biol Crystallogr,
65,
332-338.
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PDB code:
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T.Monecke,
A.Dickmanns,
and
R.Ficner
(2009).
Structural basis for m7G-cap hypermethylation of small nuclear, small nucleolar and telomerase RNA by the dimethyltransferase TGS1.
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Nucleic Acids Res,
37,
3865-3877.
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PDB code:
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T.Monecke,
T.Güttler,
P.Neumann,
A.Dickmanns,
D.Görlich,
and
R.Ficner
(2009).
Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP.
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Science,
324,
1087-1091.
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PDB code:
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X.Dong,
A.Biswas,
K.E.Süel,
L.K.Jackson,
R.Martinez,
H.Gu,
and
Y.M.Chook
(2009).
Structural basis for leucine-rich nuclear export signal recognition by CRM1.
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Nature,
458,
1136-1141.
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PDB codes:
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X.Dong,
A.Biswas,
and
Y.M.Chook
(2009).
Structural basis for assembly and disassembly of the CRM1 nuclear export complex.
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Nat Struct Mol Biol,
16,
558-560.
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G.Mitrousis,
A.S.Olia,
N.Walker-Kopp,
and
G.Cingolani
(2008).
Molecular basis for the recognition of snurportin 1 by importin beta.
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J Biol Chem,
283,
7877-7884.
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PDB codes:
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R.Worch,
and
R.Stolarski
(2008).
Stacking efficiency and flexibility analysis of aromatic amino acids in cap-binding proteins.
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Proteins,
71,
2026-2037.
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A.Cook,
F.Bono,
M.Jinek,
and
E.Conti
(2007).
Structural biology of nucleocytoplasmic transport.
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Annu Rev Biochem,
76,
647-671.
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J.Rino,
T.Carvalho,
J.Braga,
J.M.Desterro,
R.Lührmann,
and
M.Carmo-Fonseca
(2007).
A stochastic view of spliceosome assembly and recycling in the nucleus.
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PLoS Comput Biol,
3,
2019-2031.
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T.Kubota,
S.Maezawa,
K.Koiwai,
T.Hayano,
and
O.Koiwai
(2007).
Identification of functional domains in TdIF1 and its inhibitory mechanism for TdT activity.
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Genes Cells,
12,
941-959.
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J.K.Ospina,
G.B.Gonsalvez,
J.Bednenko,
E.Darzynkiewicz,
L.Gerace,
and
A.G.Matera
(2005).
Cross-talk between snurportin1 subdomains.
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Mol Biol Cell,
16,
4660-4671.
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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
