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

研究成果: ジャーナルへの寄稿学術誌査読

71 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1029-1040
ページ数12
ジャーナルStructure
2
11
DOI
出版ステータス出版済み - 11月 1994
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 構造生物学
  • 分子生物学

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