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

Daisuke Kohda, Hiroaki Terasawa, Saori Ichikawa, Kenji Ogura, Hideki Hatanaka, Valsan Mandiyan, Axel Ullrich, Joseph Schlessinger, Fuyuhiko Inagaki

Research output: Contribution to journalArticle

65 Citations (Scopus)

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 β-strands arranged in two β-sheets that are packed together perpendicularly with two additional β-strands forming the third β-sheet. GRB2 C-SH3 is very similar to SH3 domains from other proteins. The binding site of the ligand peptide (VPPPVPPRRR) 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. Conclusion 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.

Original languageEnglish
Pages (from-to)1029-1040
Number of pages12
JournalStructure
Volume2
Issue number11
DOIs
Publication statusPublished - Jan 1 1994

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GRB2 Adaptor Protein
src Homology Domains
Binding Sites
Ligands
Protein C
Son of Sevenless Proteins
Signal Transduction
Peptides
Growth Factor Receptors
Sequence Alignment
Proteins
Magnetic Resonance Spectroscopy

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

Kohda, D., Terasawa, H., Ichikawa, S., Ogura, K., Hatanaka, H., Mandiyan, V., ... Inagaki, F. (1994). Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. Structure, 2(11), 1029-1040. https://doi.org/10.1016/S0969-2126(94)00106-5

Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. / Kohda, Daisuke; Terasawa, Hiroaki; Ichikawa, Saori; Ogura, Kenji; Hatanaka, Hideki; Mandiyan, Valsan; Ullrich, Axel; Schlessinger, Joseph; Inagaki, Fuyuhiko.

In: Structure, Vol. 2, No. 11, 01.01.1994, p. 1029-1040.

Research output: Contribution to journalArticle

Kohda, D, Terasawa, H, Ichikawa, S, Ogura, K, Hatanaka, H, Mandiyan, V, Ullrich, A, Schlessinger, J & Inagaki, F 1994, 'Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2', Structure, vol. 2, no. 11, pp. 1029-1040. https://doi.org/10.1016/S0969-2126(94)00106-5
Kohda, Daisuke ; Terasawa, Hiroaki ; Ichikawa, Saori ; Ogura, Kenji ; Hatanaka, Hideki ; Mandiyan, Valsan ; Ullrich, Axel ; Schlessinger, Joseph ; Inagaki, Fuyuhiko. / Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. In: Structure. 1994 ; Vol. 2, No. 11. pp. 1029-1040.
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AU - Hatanaka, Hideki

AU - Mandiyan, Valsan

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N2 - 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 β-strands arranged in two β-sheets that are packed together perpendicularly with two additional β-strands forming the third β-sheet. GRB2 C-SH3 is very similar to SH3 domains from other proteins. The binding site of the ligand peptide (VPPPVPPRRR) 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. Conclusion 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.

AB - 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 β-strands arranged in two β-sheets that are packed together perpendicularly with two additional β-strands forming the third β-sheet. GRB2 C-SH3 is very similar to SH3 domains from other proteins. The binding site of the ligand peptide (VPPPVPPRRR) 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. Conclusion 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.

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