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PDBsum entry 1ee4
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Transport protein
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PDB id
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1ee4
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha.
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Authors
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E.Conti,
J.Kuriyan.
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Ref.
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Structure, 2000,
8,
329-338.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Karyopherin alpha (importin alpha) is an adaptor molecule that
recognizes proteins containing nuclear localization signals (NLSs). The
prototypical NLS that is able to bind to karyopherin alpha is that of the SV40 T
antigen, and consists of a short positively charged sequence motif. Distinct
classes of NLSs (monopartite and bipartite) have been identified that are only
partly conserved with respect to one another but are nevertheless recognized by
the same receptor. RESULTS: We report the crystal structures of two peptide
complexes of yeast karyopherin alpha (Kapalpha): one with a human c-myc NLS
peptide, determined at 2.1 A resolution, and one with a Xenopus nucleoplasmin
NLS peptide, determined at 2.4 A resolution. Analysis of these structures
reveals the determinants of specificity for the binding of a relatively
hydrophobic monopartite NLS and of a bipartite NLS peptide. The peptides bind
Kapalpha in its extended surface groove, which presents a modular array of
tandem binding pockets for amino acid residues. CONCLUSIONS: Monopartite and
bipartite NLSs bind to a different number of amino acid binding pockets and make
different interactions within them. The relatively hydrophobic monopartite c-myc
NLS binds extensively at a few binding pockets in a similar manner to that of
the SV40 T antigen NLS. In contrast, the bipartite nucleoplasmin NLS engages the
whole array of pockets with individually more limited but overall more abundant
interactions, which include the NLS two basic clusters and the backbone of its
non-conserved linker region. Versatility in the specific recognition of NLSs
relies on the modular.
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Figure 2.
Figure 2. Interactions of distinct NLSs with Kapa. The NLS
peptides (shown in colour) nestle between the conserved Trp-Asn
pairs of residues that line the surface of Kapa. Each pair is
provided by a single ARM repeat, shaping the regularly spaced P
and P' specificity pockets at the large and small binding sites,
respectively. The polar and electrostatic interactions between
conserved protein and NLS residues are indicated with dotted
lines. (a) Schematic diagram of the interactions between the
human c-myc NLS peptide (highlighted in blue) and yeast Kapa.
The monopartite NLS binds at the large (functional) and small
sites with mainchain and sidechain interactions. (b) Schematic
diagram of the interactions between the Xenopus nucleoplasmin
NLS peptide (highlighted in pink) and protein residues. The
bipartite NLS binds along the whole surface groove with
mainchain and sidechain interactions at the small site, and with
mainly backbone interactions of the linker and the downstream
cluster.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2000,
8,
329-338)
copyright 2000.
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