9QWP

Structure of the human RalGAP2 complex

9QWP の概要

• エントリーDOI: 10.2210/pdb9qwp/pdb
• EMDBエントリー: 53422
• 分子名称: Ral GTPase-activating protein subunit alpha-2, Ral GTPase-activating protein subunit beta (2 entities in total)
• 機能のキーワード: complex, gtpase activating protein, ral, asn thumb gap, ralgap, 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: 769685.75

構造登録者

Rasche, R.,Klink, B.U.,Gatsogiannis, C.,Kuemmel, D. (登録日: 2025-04-15, 公開日: 2025-07-16, 最終更新日: 2025-08-13)

主引用文献

Rasche, R.,Klink, B.U.,Apken, L.H.,Michalke, E.,Chen, M.,Oeckinghaus, A.,Gatsogiannis, C.,Kummel, D.
Structure and mechanism of the RalGAP tumor suppressor complex.
Nat Commun, 16:7002-7002, 2025

PubMed Abstract: The RalGAP (GTPase activating protein) complexes are negative regulators of the Ral GTPases and thus crucial components that counteract oncogenic Ras signaling. However, no structural information on the architecture of this tumor suppressor complex is available hampering a mechanistic understanding of its functionality. Here, we present a cryo-EM structure of RalGAP that reveals an extended 58 nm tetrameric architecture comprising two heterodimers of the RalGAPα and RalGAPβ subunits. We show that the catalytic domain of RalGAPα requires stabilization by a unique domain of RalGAPβ, providing the molecular basis for why RalGAP complexes are obligatory heterodimers. Formation of RalGAP tetramers is not required for activity in vitro, but essential for function of the complex in vivo. Structural analysis of RalGAP subunit variants reported in cancer patients suggests effects on complex formation and thus functional relevance, emphasizing the significance of the obtained structural information for medical research.

PubMed: 40738882
DOI: 10.1038/s41467-025-61743-9

実験手法

ELECTRON MICROSCOPY (3.8 Å)