8AU4
Structural insights reveal a heterotetramer between oncogenic K-Ras4BG12V and Rgl2, a RalA/B activator
Summary for 8AU4
| Entry DOI | 10.2210/pdb8au4/pdb |
| NMR Information | BMRB: 34754 |
| Descriptor | Ral guanine nucleotide dissociation stimulator-like 2 (1 entity in total) |
| Functional Keywords | small gtpase ras signalling protein-protein interaction nmr x-ray crystallography, signaling protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 10972.41 |
| Authors | Tariq, M.,Ikeya, T.,Togashi, N.,Fairall, L.,Alejo, C.B.,Kamei, S.,Alonso, B.R.,Campillo, M.A.M.,Hudson, A.,Ito, Y.,Schwabe, J.,Dominguez, C.,Tanaka, K. (deposition date: 2022-08-25, release date: 2023-08-23, Last modification date: 2023-10-25) |
| Primary citation | Tariq, M.,Ikeya, T.,Togashi, N.,Fairall, L.,Kamei, S.,Mayooramurugan, S.,Abbott, L.R.,Hasan, A.,Bueno-Alejo, C.,Sukegawa, S.,Romartinez-Alonso, B.,Muro Campillo, M.A.,Hudson, A.J.,Ito, Y.,Schwabe, J.W.,Dominguez, C.,Tanaka, K. Structural insights into the complex of oncogenic KRas4B G12V and Rgl2, a RalA/B activator. Life Sci Alliance, 7:-, 2024 Cited by PubMed Abstract: About a quarter of total human cancers carry mutations in Ras isoforms. Accumulating evidence suggests that small GTPases, RalA, and RalB, and their activators, Ral guanine nucleotide exchange factors (RalGEFs), play an essential role in oncogenic Ras-induced signalling. We studied the interaction between human KRas4B and the Ras association (RA) domain of Rgl2 (Rgl2), one of the RA-containing RalGEFs. We show that the G12V oncogenic KRas4B mutation changes the interaction kinetics with Rgl2 The crystal structure of the KRas4B: Rgl2 complex shows a 2:2 heterotetramer where the switch I and switch II regions of each KRas interact with both Rgl2 molecules. This structural arrangement is highly similar to the HRas:RALGDS crystal structure and is distinct from the well-characterised Ras:Raf complex. Interestingly, the G12V mutation was found at the dimer interface of KRas4B with its partner. Our study reveals a potentially distinct mode of Ras:effector complex formation by RalGEFs and offers a possible mechanistic explanation for how the oncogenic KRas4B hyperactivates the RalA/B pathway. PubMed: 37833074DOI: 10.26508/lsa.202302080 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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