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PDBsum entry 1k11
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Cell adhesion
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PDB id
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1k11
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References listed in PDB file
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Key reference
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Title
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Molecular basis for interaction between icap1 alpha ptb domain and beta 1 integrin.
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Authors
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D.D.Chang,
B.Q.Hoang,
J.Liu,
T.A.Springer.
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Ref.
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J Biol Chem, 2002,
277,
8140-8145.
[DOI no: ]
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PubMed id
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Abstract
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Icap1 alpha is a 200-amino acid protein that binds to the COOH-terminal 13 amino
acids ((786)AVTTVVNPKYEGK(798)) of the integrin beta(1) subunit. Alanine
scanning mutagenesis of this region revealed that Val(787), Val(790), and
(792)NPKY(795) are critical for Icap1 alpha binding. The NPXY motif is a known
binding substrate for phosphotyrosine binding (PTB) domain proteins. The
sequences of Icap1 alpha, residues 58--200, and the beta(1) integrin, residues
786-797, were aligned to the available PTB-peptide structures to generate a high
quality structural model. Site-directed mutagenesis showed that Leu(135),
Ile(138), and Ile(139) of Icap1 alpha, residues predicted by the model to be in
close proximity to (792)NPKY(795), and Leu(82) and Tyr(144), residues expected
to form a hydrophobic pocket near Val(787), are required for the Icap1
alpha-beta(1) integrin interaction. These findings indicate that Icap1 alpha is
a PTB domain protein, which recognizes the NPXY motif of beta(1) integrin.
Furthermore, our date suggest that an interaction between Val(787) and the
hydrophobic pocket created by Leu(82) and Tyr(144) of Icap1 alpha forms the
basis for the specificity of Icap1 alpha for the beta(1) integrin subunit.
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Figure 3.
Fig. 3. Ribbon diagram of the model of the Icap1  PTB domain
complexed with  [1] peptide.
The PTB domain is shown as a yellow ribbon; the bound [1] peptide
is shown as a pink C trace. Side
chains of key residues are shown with bonds in the same color as
the backbone, and atoms are shown in green (carbon), and red
(oxygen). Similar to other PTB domains, the Icap1 PTB domain
shares a common pleckstrin homology domain fold with a compact
central sandwich
with a COOH-terminal -helix. The
[1] peptide
forms an anti-parallel -strand with
the [5] strand
of Icap1 PTB. Key
residues on the [1] peptide
(Val787, Asn792, and Tyr795) and Icap1 (Leu82,
Leu86, Leu135, Ile^138, Ile^139, and Tyr144) are shown with side
chains. This figure was prepared with Ribbons (50).
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Figure 5.
Fig. 5. Subcellular localization of [1] integrin
with V787A mutation. NIH3T3 cells induced with human [1] integrin
(wild type, w. t.) or human [1] integrin
with alanine substitution at the Val787 position (V787A) were
plated on fibronectin-coated glass coverslips and stained with
the TS2/16 mAb.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
8140-8145)
copyright 2002.
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