4K81

Crystal structure of the Grb14 RA and PH domains in complex with GTP-loaded H-Ras

4K81 の概要

• エントリーDOI: 10.2210/pdb4k81/pdb
• 分子名称: Growth factor receptor-bound protein 14, GTPase HRas, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: adaptor protein, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q14449; Cell membrane. Isoform 2: Nucleus: P01112
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 200286.27

構造登録者

Qamra, R.,Hubbard, S.R. (登録日: 2013-04-17, 公開日: 2013-09-04, 最終更新日: 2023-09-20)

主引用文献

Qamra, R.,Hubbard, S.R.
Structural basis for the interaction of the adaptor protein grb14 with activated ras.
Plos One, 8:e72473-e72473, 2013

PubMed Abstract: Grb14, a member of the Grb7-10-14 family of cytoplasmic adaptor proteins, is a tissue-specific negative regulator of insulin signaling. Grb7-10-14 contain several signaling modules, including 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 (SH2) domain. We showed previously that the RA and PH domains, along with the BPS region and SH2 domain, are necessary for downregulation of insulin signaling. Here, we report the crystal structure at 2.4-Å resolution of the Grb14 RA and PH domains in complex with GTP-loaded H-Ras (G12V). The structure reveals that the Grb14 RA and PH domains form an integrated structural unit capable of binding simultaneously to small GTPases and phosphoinositide lipids. The overall mode of binding of the Grb14 RA domain to activated H-Ras is similar to that of the RA domains of RalGDS and Raf1 but with important distinctions. The integrated RA-PH structural unit in Grb7-10-14 is also found in a second adaptor family that includes Rap1-interacting adaptor molecule (RIAM) and lamellipodin, proteins involved in actin-cytoskeleton rearrangement. The structure of Grb14 RA-PH in complex with H-Ras represents the first detailed molecular characterization of tandem RA-PH domains bound to a small GTPase and provides insights into the molecular basis for specificity.

PubMed: 23967305
DOI: 10.1371/journal.pone.0072473

実験手法

X-RAY DIFFRACTION (2.4 Å)