9QU1
Crystal structure of the human RalGAPA2 N-terminal domain with human kappaB-Ras1
Summary for 9QU1
| Entry DOI | 10.2210/pdb9qu1/pdb |
| Descriptor | Ral GTPase-activating protein subunit alpha-2, NF-kappa-B inhibitor-interacting Ras-like protein 1, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (5 entities in total) |
| Functional Keywords | ral, gtpase, ralgap, kb-ras, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 100570.02 |
| Authors | |
| 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 Cited by 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: 40619001DOI: 10.1016/j.jbc.2025.110460 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.72 Å) |
Structure validation
Download full validation report
