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PDBsum entry 1f3c
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Contractile protein
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PDB id
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1f3c
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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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Structural basis of diverse sequence-Dependent target recognition by the 8 kda dynein light chain.
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Authors
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J.Fan,
Q.Zhang,
H.Tochio,
M.Li,
M.Zhang.
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Ref.
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J Mol Biol, 2001,
306,
97.
[DOI no: ]
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PubMed id
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Abstract
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Dyneins are multi-subunit molecular motors that translocate molecular cargoes
along microtubules. Other than acting as an essential component of the dynein
motor complex, the 89-residue subunit of dynein light chain (DLC8) also
regulates a number of other biological events by binding to various proteins and
enzymes. Currently known DLC8 targets include neuronal nitric oxide synthase;
the proapoptotic Bcl-2 family member protein designated Bim; a Drosophila RNA
localization protein Swallow, myosin V, neuronal scaffolding protein GKAP, and
IkappaBalpha, an inhibitor of the NFkappaB transcription factor. The
DLC8-binding domains of the various targets are confined within a short,
continuous stretch of amino acid residues. However, these domains do not share
any obvious sequence homology with each other. Here, the three-dimensional
structures of DLC8 complexed with two peptides corresponding to the DLC8-binding
domains of neuronal nitric oxide synthase and Bim, respectively, were determined
by NMR spectroscopy. Although the two DLC8-binding peptides have entirely
different amino acid sequences, both peptides bind to the protein with a
remarkable similar conformation by engaging the symmetric DLC8 dimer through
antiparallel beta-sheet augmentation via the beta2 strand of the protein.
Structural comparison indicates that the two target peptides use different
regions within the conformational flexible peptide-binding channels to achieve
binding specificity. We have also re-determined the apo-form solution structure
of DLC8 in this work. The structures of the DLC8/target peptide complexes,
together with the dynamic properties of the protein, provide a molecular basis
of DLC8's diverse amino acid sequence-dependent target recognition.
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Figure 3.
Figure 3. Comparison of the
interactions of DLC8 with the Bim
peptide and the nNOS peptide.
Stereoview representations of (a)
the Bim peptide; and (b) the nNOS
peptide binding grooves of DLC8.
For clarity, only the regions of
DLC8 that are directly involved in
the binding are included in the
figure. In (a) and (b) the target pep-
tides are shown using explicit atom
representations in magenta. Amino
acid residues in DLC8 that make
key contacts with the peptides are
also shown in the Figure. Due to
its irregular strand structure, the b0
strand of DLC8 is also shown
using explicit atom representations
(yellow). (b) The distance between
the oxygen atom of the Thr4
hydroxyl group of the nNOS pep-
tide and the N
e
of His68 is also
indicated. (c) Schematic showing
the b-strand pairing between the b2
strand of DLC8 and the b strand of
the nNOS peptide and the Bim
peptide. The amino acid residues
that adopt b-strand structure are
highlighted by arrows. The amino
acid residues in the b-strands with
their side-chains pointing to the
dimer interface are shaded.
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Figure 6.
Figure 6. Identification of critical amino acid residues
in the nNOS peptide for DLC8 binding. The amino acid
sequence of the DLC8-binding region of the nNOS pep-
tide (residues 1 to 12) is shown in the first row. Each
mutation prepared in this study is shown in the sub-
sequent rows. The DLC8-binding assay results, derived
from the ``pull-down'' experiments, are shown at the
right side of the Figure.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2001,
306,
97-0)
copyright 2001.
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