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PDBsum entry 2qna
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Transport protein
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PDB id
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2qna
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References listed in PDB file
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Key reference
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Title
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Structural basis for rangtp independent entry of spliceosomal u snrnps into the nucleus.
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Authors
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D.Wohlwend,
A.Strasser,
A.Dickmanns,
R.Ficner.
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Ref.
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J Mol Biol, 2007,
374,
1129-1138.
[DOI no: ]
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PubMed id
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Abstract
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The nuclear import of assembled spliceosomal subunits, the uridine-rich small
nuclear ribonucleoprotein particles (U snRNPs), is mediated by a nuclear import
receptor adaptor couple of importinbeta (Impbeta) and snurportin1 (SPN1). In
contrast to any other characterized active nuclear import, the Impbeta/SPN1/U
snRNP complex does not require RanGTP for the terminal release from the nuclear
basket of the nuclear pore complex (NPC). The crystal structure of Impbeta
(127-876) in complex with the Impbeta-binding (IBB) domain of SPN1 (1-65) at
2.8-A resolution reveals that Impbeta adopts an open conformation, which is
unique for a functional Impbeta/cargo complex, and rather surprisingly, it
resembles the conformation of the Impbeta/RanGTP complex. As binding of RanGTP
to Impbeta usually triggers the release of import complexes from the NPC, we
propose that by already mimicking a conformation similar to Impbeta/RanGTP the
independent dissociation of Impbeta/SPN1 from the nuclear basket is
energetically aided.
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Figure 1.
Fig. 1. Structure of Impβ in complex with IBB[SPN1]. (a)
Overall structure of Impβ/IBB[SPN1], with a view into the
C-terminal cavity. The IBB domain of SPN1 is depicted in red,
the N-terminal arch of Impβ, which is not involved in the
interaction is shown in blue, the C-terminal arch, binding to
IBB[SPN1], is shown in green. (b) Structure rotated by 90°,
with view from the C terminus of Impβ; colouring as in (a).
HEAT 13B, illustrated in yellow, is inclined toward IBB[SPN1].
(c) and (d) Detailed view into interactions between
Impβ_127–876 and IBB[SPN1]; colouring as in (a). Side chains
involved in binding are depicted as ball and stick
presentations. (c) View from the top of the C-terminal arch of
Impβ. (d) View from the bottom of the C-terminal arch. (e) and
(f) Electron density presentations of the environments of two
arginines of IBB[SPN1], which interact with Impβ_127–876.
Dotted lines mark hydrogen bonds. (e) The hydrogen bond network
with Arg43 of IBB[SPN1] as center involves Cys585, Asp627 and
Met630 of Impβ; in close vicinity is Gln40 of IBB[SPN1],
forming an intramolecular hydrogen bond. (f) Arg63 not only is
bound to Gly820 with a single bond and to Asp824 via a bidentite
hydrogen bond, but also coordinates a water molecule that is
involved in the hydration shell of Impβ.
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Figure 3.
Fig. 3. The overall conformation of Impβ in complex with
IBB[SPN1] and IBB[α], respectively, differs significantly. (a)
Superposition of the structures of Impβ/IBB[SPN1] (blue) and
Impβ/IBB[α] (red). Only Impβ is shown in each case. The
superposition reveals a considerable difference of 14 Å in
the dilatation of both molecules. The distances between Asn141
and Ala876 were measured and are indicated. (b) Comparison
between a homology amino acid sequence alignment^17 and a
structure-based sequence alignment of IBB[α] and IBB[SPN1]
derived from the crystal structures of Impβ/IBB[α] and
Impβ/IBB[SPN1]: Green boxes indicate functionally conserved
residues regarding interaction with Impβ; red boxes mark
residues of IBB[α] that interact with the acidic loop of Impβ.
They also mark the corresponding amino acids of IBB[SPN1]
according to Ref. 9.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
374,
1129-1138)
copyright 2007.
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