8AU4

Structural insights reveal a heterotetramer between oncogenic K-Ras4BG12V and Rgl2, a RalA/B activator

8AU4 の概要

• エントリーDOI: 10.2210/pdb8au4/pdb
• NMR情報: BMRB: 34754
• 分子名称: Ral guanine nucleotide dissociation stimulator-like 2 (1 entity in total)
• 機能のキーワード: small gtpase ras signalling protein-protein interaction nmr x-ray crystallography, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10972.41

構造登録者

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. (登録日: 2022-08-25, 公開日: 2023-08-23, 最終更新日: 2023-10-25)

主引用文献

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

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: 37833074
DOI: 10.26508/lsa.202302080

実験手法

SOLUTION NMR