PDBsum entry 1gfd

Adaptor protein containing sh2 and sh3

PDB id: 1gfd

Contents

Protein chain

59 a.a. *

* Residue conservation analysis

PDB id:

1gfd

Name:

Adaptor protein containing sh2 and sh3

Title:

Solution structure and ligand-binding site of thE C-terminal sh3 domain of grb2

Structure:

Growth factor receptor-bound protein 2. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: grb2

NMR struc:

20 models

Authors:

D.Kohda,H.Terasawa,H.Hatanaka,F.Inagaki

Key ref:

D.Kohda et al. (1994). Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. Structure, 2, 1029-1040. PubMed id: 7881903 DOI: 10.1016/S0969-2126(94)00106-5

Date:

13-Jun-94 Release date: 31-Aug-94

Protein chain

P62993  (GRB2_HUMAN) -  Growth factor receptor-bound protein 2 from Homo sapiens

Seq: 217 a.a.

Struc: 59 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/S0969-2126(94)00106-5

Structure 2:1029-1040 (1994)

PubMed id: 7881903

Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2.

D.Kohda, H.Terasawa, S.Ichikawa, K.Ogura, H.Hatanaka, V.Mandiyan, A.Ullrich, J.Schlessinger, F.Inagaki.

ABSTRACT

BACKGROUND: Growth factor receptor-bound protein 2 (GRB2) is an adaptor protein with three Src homology (SH) domains in the order SH3-SH2-SH3. Both SH3 domains of GRB2 are necessary for interaction with the protein Son of sevenless (Sos), which acts as a Ras activator. Thus, GRB2 mediates signal transduction from growth factor receptors to Ras and is thought to be a key molecule in signal transduction. RESULTS: The three-dimensional structure of the carboxy-terminal SH3 domain of GRB2 (GRB2 C-SH3) was determined by NMR spectroscopy. The SH3 structure consists of six beta-strands arranged in two beta-sheets that are packed together perpendicularly with two additional beta-strands forming the third beta-sheet. GRB2 C-SH3 is very similar to SH3 domains from other proteins. The binding site of the ligand peptide (VPP-PVPPRRR) derived from the Sos protein was mapped on the GRB2 C-SH3 domain indirectly using 1H and 15N chemical shift changes, and directly using several intermolecular nuclear Overhauser effects. CONCLUSIONS: Despite the structural similarity among the known SH3 domains, the sequence alignment and the secondary structure assignments differ. We therefore propose a standard description of the SH3 structures to facilitate comparison of individual SH3 domains, based on their three-dimensional structures. The binding site of the ligand peptide on GRB2 C-SH3 is in good agreement with those found in other SH3 domains.

Selected figure(s)

Figure 6.
Figure 6. Schematic representation of GRB2 C–SH3 and other SH3 domains. The βI–sheet is drawn in red, the βII–sheet is in blue, the βIII–sheet is in green, the 3[10]–helix is in magenta, and the rest is in white. PI3K SH3 was drawn using the coordinates of bovine PI3K. The ribbon diagrams in Fig 6 and Figure8 were generated using the program MOLSCRIPT [52]. Figure 6. Schematic representation of GRB2 C–SH3 and other SH3 domains. The βI–sheet is drawn in red, the βII–sheet is in blue, the βIII–sheet is in green, the 3[10]–helix is in magenta, and the rest is in white. PI3K SH3 was drawn using the coordinates of bovine PI3K. The ribbon diagrams in Fig 6 and [3]Figure8 were generated using the program MOLSCRIPT [[4]52].

Figure 8.
Figure 8. The overlay of the backbone atoms of the 38 residues found in regions of the conserved secondary structures, The SH3 structures superimposed are GRB2 C–SH3 (white), PLCγ (yellow), spectrin (red), Fyn (purple), Src (green) and bovine PI3K (blue). The structures are in the same orientation as in Figure 2a. Figure 8. The overlay of the backbone atoms of the 38 residues found in regions of the conserved secondary structures, The SH3 structures superimposed are GRB2 C–SH3 (white), PLCγ (yellow), spectrin (red), Fyn (purple), Src (green) and bovine PI3K (blue). The structures are in the same orientation as in [3]Figure 2a.

The above figures are reprinted by permission from Cell Press: Structure (1994, 2, 1029-1040) copyright 1994.

Figures were selected by an automated process.