3HK0

Crystal Structure of the RA and PH Domains of Grb10

3HK0 の概要

• エントリーDOI: 10.2210/pdb3hk0/pdb
• 分子名称: Growth factor receptor-bound protein 10, THIOCYANATE ION (3 entities in total)
• 機能のキーワード: grb10, ra, ph, ras-associating, pleckstrin-homology, adapter protein, phosphoprotein, sh2 domain, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): Q13322
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59059.48

構造登録者

Hubbard, S.R.,Depetris, R.S.,Wu, J. (登録日: 2009-05-22, 公開日: 2009-08-04, 最終更新日: 2024-02-21)

主引用文献

Depetris, R.S.,Wu, J.,Hubbard, S.R.
Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14.
Nat.Struct.Mol.Biol., 16:833-839, 2009

PubMed Abstract: Growth factor receptor-binding proteins Grb7, Grb10 and Grb14 are adaptor proteins containing a Ras-associating (RA) domain, a pleckstrin-homology (PH) domain, a family-specific BPS (between PH and SH2) region and a C-terminal Src-homology-2 domain. Previous structural studies showed that the Grb14 BPS region binds as a pseudosubstrate inhibitor in the tyrosine kinase domain of the insulin receptor to suppress insulin signaling. Here we report the crystal structure of the RA and PH domains of Grb10 at 2.6-A resolution. The structure reveals that these two domains, along with the intervening linker, form an integrated, dimeric structural unit. Biochemical studies demonstrated that Grb14 binds to activated Ras, which may serve as a timing mechanism for downregulation of insulin signaling. Our results illuminate the membrane-recruitment mechanisms not only of Grb7, Grb10 and Grb14 but also of MIG-10, Rap1-interacting adaptor molecule, lamellipodin and Pico, proteins involved in actin-cytoskeleton rearrangement that share a structurally related RA-PH tandem unit.

PubMed: 19648926
DOI: 10.1038/nsmb.1642

実験手法

X-RAY DIFFRACTION (2.6 Å)