PDBsum entry 1h3h

Protein binding

PDB id: 1h3h

Contents

Protein chains

60 a.a. *

11 a.a. *

* Residue conservation analysis

PDB id:

1h3h

Name:

Protein binding

Title:

Structural basis for specific recognition of an rxxk-containing slp-76 peptide by the gads c-terminal sh3 domain

Structure:

Grb2-related adaptor protein 2. Chain: a. Fragment: c-terminal sh3 domain, residues 263-322. Synonym: gads protein, grblg, grb2l. Engineered: yes. Lymphocyte cytosolic protein 2. Chain: b. Fragment: residues 226-235. Synonym: slp-76.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Cell: t-lymphocyte. Expressed in: escherichia coli. Expression_system_taxid: 469008. Homo sapiens. Human. Organism_taxid: 9606.

NMR struc:

20 models

Authors:

Q.Liu,D.Berry,P.Nash,T.Pawson,C.J.Mcglade,S.S.Li

Key ref:

Q.Liu et al. (2003). Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition. Mol Cell, 11, 471-481. PubMed id: 12620234 DOI: 10.1016/S1097-2765(03)00046-7

Date:

03-Sep-02 Release date: 06-Mar-03

Protein chain

O89100  (GRAP2_MOUSE) -  GRB2-related adaptor protein 2 from Mus musculus

Seq: 322 a.a.

Struc: 60 a.a.

Protein chain

Q13094  (LCP2_HUMAN) -  Lymphocyte cytosolic protein 2 from Homo sapiens

Seq: 533 a.a.

Struc: 11 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1016/S1097-2765(03)00046-7

Mol Cell 11:471-481 (2003)

PubMed id: 12620234

Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition.

Q.Liu, D.Berry, P.Nash, T.Pawson, C.J.McGlade, S.S.Li.

ABSTRACT

The SH3 domain, which normally recognizes proline-rich sequences, has the potential to bind motifs with an RxxK consensus. To explore this novel specificity, we have determined the solution structure of the Gads T cell adaptor C-terminal SH3 domain in complex with an RSTK-containing peptide, representing its physiological binding site on the SLP-76 docking protein. The SLP-76 peptide engages four distinct binding pockets on the surface of the Gads SH3 domain and upon binding adopts a unique structure characterized by a right-handed 3(10) helix at the RSTK locus, in contrast to the left-handed polyproline type II helix formed by canonical proline-rich SH3 ligands. The structure, and supporting mutagenesis and peptide binding data, reveal a novel mode of ligand recognition by SH3 domains.

Selected figure(s)

Figure 1.
Figure 1. Solution Structure of a Gads SH3-C Domain – SLP-76 Peptide Complex(A) Stereo view of a superposition of 20 lowest-energy structures of the Gads SH3-C domain – SLP-76 peptide complex in backbone traces. The Gads SH3-C domain (residues 265–321) is shown in green and the SLP-76 peptide in violet. The peptide has the sequence A^1PSIDRSTKPA^11, of which the first ten residues were taken from the Gads SH3-C – binding site in SLP-76, and the last Ala was added to reduce end effects. Ala11 does not interact with the SH3 domain (see Figure 3B) and is hence omitted from all figures for clarity.(B) Ribbon representation of the same complex generated using coordinates of the lowest-energy structure. The β strands and the RT- and n-Src loops of the SH3 domain are labeled in black. The peptide backbone is depicted in violet with side chains shown in pale green or dark green (for residues located at the peptide-protein interface).

Figure 2.
Figure 2. A Comparison of Peptide Binding Surfaces between the Gads and c-Src SH3 Domains(A) Surface representation of the Gads SH3-C domain – SLP-76 peptide complex. Areas of positive and negative charges are shown in blue and red, respectively. Residues in the peptides that occupy the four binding pockets on the SH3 domain surface (identified in dotted circles) are labeled in black. Residue Glu275 of the protein, which encloses the second pocket, is labeled in red.(B) Surface representation of the c-Src SH3 domain – APP12 peptide complex (adapted from Feng et al., 1995). APP12 is a dodecapeptide that binds with high affinity to the c-Src SH3 domain (Kd = 1.2 μM). Since the last four residues of the peptide do not contribute significantly to SH3 binding (Feng et al., 1995), only the first eight residues of the peptide (A^1PPLPPRN^8) are shown for clarity. As in (A), key residues in peptide APP12 that engage the three binding pockets (identified as dotted circles) on the c-Src SH3 domain are labeled.

The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 11, 471-481) copyright 2003.

Figures were selected by an automated process.