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PDBsum entry 1miz
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Structural protein
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PDB id
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1miz
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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 determinants of integrin recognition by talin.
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Authors
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B.García-Alvarez,
J.M.De pereda,
D.A.Calderwood,
T.S.Ulmer,
D.Critchley,
I.D.Campbell,
M.H.Ginsberg,
R.C.Liddington.
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Ref.
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Mol Cell, 2003,
11,
49-58.
[DOI no: ]
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PubMed id
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Abstract
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The binding of cytoplasmic proteins, such as talin, to the cytoplasmic domains
of integrin adhesion receptors mediates bidirectional signal transduction. Here
we report the crystal structure of the principal integrin binding and activating
fragment of talin, alone and in complex with fragments of the beta 3 integrin
tail. The FERM (four point one, ezrin, radixin, and moesin) domain of talin
engages integrins via a novel variant of the canonical phosphotyrosine binding
(PTB) domain-NPxY ligand interaction that may be a prototype for FERM domain
recognition of transmembrane receptors. In combination with NMR and mutational
analysis, our studies reveal the critical interacting elements of both talin and
the integrin beta 3 tail, providing structural paradigms for integrin linkage to
the cell interior.
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Figure 3.
Figure 3. Comparison of FERM F3 and PTB Domain
InteractionsStereo Cα plot comparing the F3 subdomain of talin
and the integrin sequence (red), the F3 subdomain of moesin and
the β strand of the C-terminal tail (green), and the PTB domain
of X11 with the β-APP bound (blue). The structures were
superposed by aligning the Cα atoms of 39 residues in the β
sandwich. The ligands are shown as thick lines. The tyrosine
sidechains of the NPxY motifs of integrin and β-APP are also
shown. For clarity, insertions in the X11 structure absent in
FERM domains are not shown. Residue numbering is for talin.
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Figure 4.
Figure 4. Structure-Based Mutagenesis of the TalinAt left,
binding of talin mutants to full-length β3 tail. Recombinant
F2+F3 containing the indicated mutation was incubated with the
integrin β3 cytoplasmic domain model protein; following
washing, the bound protein was detected by SDS-PAGE. Note the
absence of binding to β3(Y747A) and αIIb cytoplasmic domain
model proteins and the equal loading (rightmost column) of each
mutant. The bottom row depicts the equal loading of each model
tail protein as judged by SDS-PAGE. At right, residues mutated
in this study are mapped onto the surface of the talin F3
domain, with hydrophobic residues colored yellow. The K357A
mutation (green) does not affect binding, while alanine
substitution of R358, W359, and I396 (red) reduce binding.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2003,
11,
49-58)
copyright 2003.
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