9QU1

Crystal structure of the human RalGAPA2 N-terminal domain with human kappaB-Ras1

9QU1 の概要

• エントリーDOI: 10.2210/pdb9qu1/pdb
• 分子名称: Ral GTPase-activating protein subunit alpha-2, NF-kappa-B inhibitor-interacting Ras-like protein 1, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: ral, gtpase, ralgap, kb-ras, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 100570.02

構造登録者

Rasche, R.,Kuemmel, D. (登録日: 2025-04-09, 公開日: 2025-07-16)

主引用文献

Rasche, R.,Apken, L.H.,Titze, S.,Michalke, E.,Singh, R.K.,Oeckinghaus, A.,Kummel, D.
The GTPase kappa B-Ras is an essential subunit of the RalGAP tumor suppressor complex.
J.Biol.Chem., :110460-110460, 2025

PubMed Abstract: κB-Ras1 and κB-Ras2 are small GTPases with non-canonical features that act as tumor suppressors downstream of Ras. Via interaction with the RalGAP (GTPase activating protein) complex, they limit activity of Ral GTPases and restrict anchorage-independent proliferation. We here present the crystal structure of κB-Ras1 in complex with the N-terminal domain of RGα2. The structure suggests a mechanism of intrinsic GTP hydrolysis of κB-Ras1 that relies on a scaffolding function of the GTPase rather than on catalytic residues, which we confirm by mutational analysis. The interaction with RGα2 is nucleotide-independent and does not involve κB-Ras1 switch regions, which establishes κB-Ras proteins as a constitutive third subunit of RalGAP complexes. Functional studies demonstrate that κB-Ras proteins are not required for RalGAP catalytic activity in vitro, but for functionality in vivo. We propose that κB-Ras may thus act as regulator of RalGAP localization and thereby control the Ras/Ral signaling pathway.

PubMed: 40619001
DOI: 10.1016/j.jbc.2025.110460

実験手法

X-RAY DIFFRACTION (2.72 Å)