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PDBsum entry 1mq1
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Metal binding protein
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PDB id
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1mq1
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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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A novel s100 target conformation is revealed by the solution structure of the ca2+-S100b-Trtk-12 complex.
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Authors
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K.A.Mcclintock,
G.S.Shaw.
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Ref.
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J Biol Chem, 2003,
278,
6251-6257.
[DOI no: ]
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PubMed id
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Abstract
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The Alzheimer-linked neural protein S100B is a signaling molecule shown to
control the assembly of intermediate filament proteins in a calcium-sensitive
manner. Upon binding calcium, a conformational change occurs in S100B exposing a
hydrophobic surface for target protein interactions. The synthetic peptide
TRTK-12 (TRTKIDWNKILS), derived from random bacteriophage library screening,
bears sequence similarity to several intermediate filament proteins and has the
highest calcium-dependent affinity of any target molecule for S100B to date
(K(d) <1 microm). In this work, the three-dimensional structure of the
Ca(2+)-S100B-TRTK-12 complex has been determined by NMR spectroscopy. The
structure reveals an extended, contiguous hydrophobic surface is formed on
Ca(2+)-S100B for target interaction. The TRTK-12 peptide adopts a coiled
structure that fits into a portion of this surface, anchored at Trp(7), and
interacts with multiple hydrophobic contacts in helices III and IV of
Ca(2+)-S100B. This interaction is strikingly different from the alpha-helical
structures found for other S100 target peptides. By using the TRTK-12
interaction as a guide, in combination with other available S100 target
structures, a recognition site on helix I is identified that may act in concert
with the TRTK-12-binding site from helices III and IV. This would provide a
larger, more complex site to interact with full-length target proteins and would
account for the promiscuity observed for S100B target protein interactions.
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Figure 2.
Fig. 2. Structure of the Ca^2+-S100B-TRTK-12 complex. The
N and C termini are labeled for one S100  monomer and
TRTK-12, and helices are indicated for S100 . A, stereo
view of the backbone superposition of the final ensemble of 17
NMR derived structures of the complex. S100 monomers are
shown in magenta and blue, and the TRTK-12 peptide molecules are
shown in light blue. B, ribbon structure of the complex. Each
monomer consists of four  -helices
(helix I, blue; II, magenta; III, green; and IV, yellow) and two
anti-parallel -strands
(orange, blue). TRTK-12 is shown in dark blue.
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Figure 5.
Fig. 5. Electrostatic potential surface showing the
TRTK-12-binding site on Ca^2+-S100B. Negative potential is
indicated in blue, and positive potential is shown in red for
Ca^2+-S100B. A, location of the two TRTK-12 molecules ( green)
on opposite sides of Ca^2+-S100B. The TRTK-12 peptide fits into
the hydrophobic cleft generated by helices III and IV of each
monomer. Note that on either side of the TRTK-12-binding site a
significant uncharged region exists. B, environment of the
anchoring Trp7 residue from TRTK-12 (green) showing interactions
with S100B residues (blue) in helix III (Val56 and Thr59) and IV
(Phe^76 and Val80).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2003,
278,
6251-6257)
copyright 2003.
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