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PDBsum entry 1qcy
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Cell adhesion
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PDB id
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1qcy
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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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Jararhagin-Derived rkkh peptides induce structural changes in alpha1i domain of human integrin alpha1beta1.
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Authors
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Y.Nymalm,
J.S.Puranen,
T.K.Nyholm,
J.Käpylä,
H.Kidron,
O.T.Pentikäinen,
T.T.Airenne,
J.Heino,
J.P.Slotte,
M.S.Johnson,
T.A.Salminen.
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Ref.
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J Biol Chem, 2004,
279,
7962-7970.
[DOI no: ]
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PubMed id
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Abstract
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Integrin alpha(1)beta(1) is one of four collagen-binding integrins in humans.
Collagens bind to the alphaI domain and in the case of alpha(2)I collagen
binding is competitively inhibited by peptides containing the RKKH sequence and
derived from the metalloproteinase jararhagin of snake venom from Bothrops
jararaca. In alpha(2)I, these peptides bind near the metal ion-dependent
adhesion site (MIDAS), where a collagen (I)-like peptide is known to bind;
magnesium is required for binding. Published structures of the ligand-bound
"open" conformation of alpha(2)I differs significantly from the
"closed" conformation seen in the structure of apo-alpha(2)I near
MIDAS. Here we show that two peptides, CTRKKHDC and CARKKHDC, derived from
jararhagin also bind to alpha(1)I and competitively inhibit collagen I binding.
Furthermore, calorimetric and fluorimetric measurements show that the structure
of the complex of alpha(1)I with Mg(2+) and CTRKKHDC differs from structure in
the absence of peptide. A comparison of the x-ray structure of apo-alpha(1)I
("closed" conformation) and a model structure of the alpha(1)I
("open" conformation) based on the closely related structure of
alpha(2)I reveals that the binding site is partially blocked to ligands by
Glu(255) and Tyr(285) in the "closed" structure, whereas in the
"open" structure helix C is unwound and these residues are shifted,
and the "RKKH" peptides fit well when docked. The "open"
conformation of alpha(2)I resulting from binding a collagen (I)-like peptide
leads to exposure of hydrophobic surface, also seen in the model of alpha(1)I
and shown experimentally for alpha(1)I using a fluorescent hydrophobic probe.
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Figure 6.
FIG. 6. Conformational changes proposed to occur in  [1]I.
Comparison of "closed" (x-ray structure) (A) and "open" (model
structure) conformations of [1]I (B). Tyr285 and
Trp158 are shown, and the metal ion at MIDAS is colored pink.
Helix 6 and helix C are colored red, whereas helix 7 is colored
blue. The model structure of the "open" conformation is based on
the close similarity with [2]I, whose structure
in the "open" form is known. Figs. 6, 7, 8 were prepared using
Molscript 2.1.2 (70), Raster3D 2.7b (49), and GIMP 1.3.20
(available on the World Wide Web at www.gimp.org). Molecular
surfaces were made using Bodil.2
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Figure 8.
FIG. 8. In comparison with the "closed" conformation, the
"open" conformation exposes localized patches of hydrophobic
surface. A, [1]I, "closed"
conformation. B, model of [1]I with bound
CTRKKHDC peptide, "open" conformation. C, [2]I, "closed"
conformation. D, [2]I with bound
collagen (I)-like peptide, "open" conformation. Residues
contributing to the patches are labeled, and their hydrophobic
atoms were colored in gray.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
7962-7970)
copyright 2004.
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