PDBsum entry 1k11

Cell adhesion

PDB id: 1k11

Contents

Protein chains

125 a.a.

12 a.a.

Theoretical model

PDB id:

1k11

Name:

Cell adhesion

Title:

Theoretical structure of icap1-alpha bound to integrin beta1 cytoplasmic domain

Structure:

Integrin cytoplasmic domain associated protein. Chain: a. Synonym: icap1-alpha. Integrin beta-1. Chain: b. Fragment: cytoplasmic domain

Source:

Homo sapiens. Human. Human

Authors:

D.D.Chang,B.Q.Hoang,J.Liu,T.A.Springer

Key ref:

D.D.Chang et al. (2002). Molecular basis for interaction between Icap1 alpha PTB domain and beta 1 integrin. J Biol Chem, 277, 8140-8145. PubMed id: 11741908 DOI: 10.1074/jbc.M109031200

Date:

22-Sep-01 Release date: 20-Mar-02

Protein chain

No UniProt id for this chain

Struc: 125 a.a.

Protein chain

P05556  (ITB1_HUMAN) -  Integrin beta-1 from Homo sapiens

Seq: 798 a.a.

Struc: 12 a.a.

DOI no: 10.1074/jbc.M109031200

J Biol Chem 277:8140-8145 (2002)

PubMed id: 11741908

Molecular basis for interaction between Icap1 alpha PTB domain and beta 1 integrin.

D.D.Chang, B.Q.Hoang, J.Liu, T.A.Springer.

ABSTRACT

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.

Selected figure(s)

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).

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.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 8140-8145) copyright 2002.

Figures were selected by an automated process.