9QWP

Structure of the human RalGAP2 complex

Summary for 9QWP

• Entry DOI: 10.2210/pdb9qwp/pdb
• EMDB information: 53422
• Descriptor: Ral GTPase-activating protein subunit alpha-2, Ral GTPase-activating protein subunit beta (2 entities in total)
• Functional Keywords: complex, gtpase activating protein, ral, asn thumb gap, ralgap, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 769685.75

Authors

Rasche, R.,Klink, B.U.,Gatsogiannis, C.,Kuemmel, D. (deposition date: 2025-04-15, release date: 2025-07-16, Last modification date: 2025-08-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.8 Å)