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PDBsum entry 1rkc
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Cell adhesion, structural protein
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PDB id
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1rkc
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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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Vinculin activation by talin through helical bundle conversion.
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Authors
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T.Izard,
G.Evans,
R.A.Borgon,
C.L.Rush,
G.Bricogne,
P.R.Bois.
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Ref.
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Nature, 2004,
427,
171-175.
[DOI no: ]
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PubMed id
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Abstract
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Vinculin is a conserved component and an essential regulator of both cell-cell
(cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions)
junctions, and it anchors these adhesion complexes to the actin cytoskeleton by
binding to talin in integrin complexes or to alpha-actinin in cadherin
junctions. In its resting state, vinculin is held in a closed conformation
through interactions between its head (Vh) and tail (Vt) domains. The binding of
vinculin to focal adhesions requires its association with talin. Here we report
the crystal structures of human vinculin in its inactive and talin-activated
states. Talin binding induces marked conformational changes in Vh, creating a
novel helical bundle structure, and this alteration actively displaces Vt from
Vh. These results, as well as the ability of alpha-actinin to also bind to Vh
and displace Vt from pre-existing Vh-Vt complexes, support a model whereby Vh
functions as a domain that undergoes marked structural changes that allow
vinculin to direct cytoskeletal assembly in focal adhesions and adherens
junctions. Notably, talin's effects on Vh structure establish helical bundle
conversion as a signalling mechanism by which proteins direct cellular responses.
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Figure 3.
Figure 3: Structure of inactive human vinculin. a, Cartoon
representation of the closed conformation of vinculin (Vh,
residues 1 -258, pink; Vt, 879 -1066, light blue). b, c,
Electrostatic surface potential (red, negative; blue, positive)
of the Vh -Vt complex. b, Head-on view of each interface (left,
Vh; right, Vt) when Vh and Vt are taken apart (that is, Vh is
rotated 90° to the left and Vt is rotated 90° to the right with
respect to the orientation shown in a). Residues involved in
interdomain contacts are labelled. c, Same orientation as in a,
revealing the acidic pocket created when Vh binds to Vt. Acidic
residues lining the pocket are indicated in yellow.
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Figure 4.
Figure 4: Structure of Vh when activated by talin. a,
Electrostatic surface potential (red, negative; blue, positive)
of Vh when bound to talin. Talin VBS3 is shown in ball-and-stick
representation (oxygen atoms, red; carbon, yellow; nitrogen,
blue; bonds, black). b, The C-terminal bundle (helices  4
-7) of active (red) and inactive (pink) Vh are superimposed
(back view of Fig. 3a). Talin VBS3, dark blue; Vt, light blue.
c, Movements and helical distortions (green arrows) of the
helices ( 1
-4) of the N-terminal bundle of inactive Vh (pink) occurring on
activation of Vh (red) by talin VBS3 (dark blue). Helices H1 -5
of inactive Vt (grey) are shown when bound to Vh (pink).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2004,
427,
171-175)
copyright 2004.
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