PDBsum entry 1i3z

Signaling protein

PDB id: 1i3z

Contents

Protein chain

103 a.a. *

Ligands

SER-LEU-THR-ILE-PTR-ALA-GLN-VAL-GLN-LYS

Waters ×86

* Residue conservation analysis

PDB id:

1i3z

Name:

Signaling protein

Title:

Murine eat2 sh2 domain in complex with slam phosphopeptide

Structure:

Ews/fli1 activated transcript 2. Chain: a. Fragment: sh2 domain (residues 1-103). Engineered: yes. Signaling lymphocytic activation molecule. Chain: b. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this peptide was chemically synthesized. The sequence of this peptide is naturally found in homo sapiens (humans).

Biol. unit:

Dimer (from PQS)

Resolution:

2.15Å R-factor: 0.219 R-free: 0.279

Authors:

J.Lu,F.Poy,M.Morra,C.Terhorst,M.J.Eck

Key ref:

M.Morra et al. (2001). Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells. EMBO J, 20, 5840-5852. PubMed id: 11689425 DOI: 10.1093/emboj/20.21.5840

Date:

19-Feb-01 Release date: 08-Apr-03

Protein chain

O35324  (SH21B_MOUSE) -  SH2 domain-containing protein 1B from Mus musculus

Seq: 132 a.a.

Struc: 103 a.a.

DOI no: 10.1093/emboj/20.21.5840

EMBO J 20:5840-5852 (2001)

PubMed id: 11689425

Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells.

M.Morra, J.Lu, F.Poy, M.Martin, J.Sayos, S.Calpe, C.Gullo, D.Howie, S.Rietdijk, A.Thompson, A.J.Coyle, C.Denny, M.B.Yaffe, P.Engel, M.J.Eck, C.Terhorst.

ABSTRACT

The T and natural killer (NK) cell-specific gene SAP (SH2D1A) encodes a 'free SH2 domain' that binds a specific tyrosine motif in the cytoplasmic tail of SLAM (CD150) and related cell surface proteins. Mutations in SH2D1A cause the X-linked lymphoproliferative disease, a primary immunodeficiency. Here we report that a second gene encoding a free SH2 domain, EAT-2, is expressed in macrophages and B lympho cytes. The EAT-2 structure in complex with a phosphotyrosine peptide containing a sequence motif with Tyr281 of the cytoplasmic tail of CD150 is very similar to the structure of SH2D1A complexed with the same peptide. This explains the high affinity of EAT-2 for the pTyr motif in the cytoplasmic tail of CD150 but, unlike SH2D1A, EAT-2 does not bind to non-phosphorylated CD150. EAT-2 binds to the phosphorylated receptors CD84, CD150, CD229 and CD244, and acts as a natural inhibitor, which interferes with the recruitment of the tyrosine phosphatase SHP-2. We conclude that EAT-2 plays a role in controlling signal transduction through at least four receptors expressed on the surface of professional antigen-presenting cells.

Selected figure(s)

Figure 1.
Figure 1 The human EAT-2 gene. (A) Alignment of the human and mouse EAT-2 nucleotide sequences. The coding region sequences of the human (hEAT-2) and mouse (mEAT-2) EAT-2 cDNAs are compared. Exon boundaries are indicated (bold font, identity of nucleotides; regular font, difference of nucleotides). (B) Genomic organization of the human EAT-2 gene. The human EAT-2 gene consists of four exons that present an overall organization similar to that of the SH2D1A gene. The putative exon IIIA represents part of exon III (see text).

Figure 4.
Figure 4 EAT-2 binds exclusively to a phosphorylated peptide (pY281) derived from the cytoplasmic tail of CD150. (A) Fluorescence polarization analysis of the EAT-2 binding to a phosphorylated pY281 peptide. Different concentrations of GST -mouse EAT-2 (or GST -human SH2D1A) and an 11mer synthetic peptide identical to amino acid residues 276 -287 of human CD150 (Sayos et al., 1998), tyrosine phosphorylated or not, were used. Top panel: binding of GST -mouse EAT-2 to the pY281 (filled triangles and continuous line) or the Y281 peptide (open squares and dashed line). Bottom panel: binding of GST -human SH2D1A to the pY281 (filled triangles and continuous line) or the Y281 peptide (open squares and dashed line). x-axis: protein concentration (nM); y-axis: polarization units (mP). The table summarizes the apparent dissociation constant (kD). (B) Hybrid system analysis of the interaction between EAT-2 and the cytoplasmic tail of CD150 in the presence or absence of fyn. Dashed bars indicate the interaction between the EAT-2 (or SH2D1A) full-length protein fused to a GAL4 DNA-binding domain and the GAL4 DNA activation domain fused to the cytoplasmic tail of the CD150 receptor. An empty pGAD424 vector was used as a control (solid bars). The test was conducted in either the presence or absence of fyn[420,531Y -F]. y-axis = -galactosidase (U/ml).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 5840-5852) copyright 2001.

Figures were selected by an automated process.