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)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.8 Å)