4M69

Crystal structure of the mouse RIP3-MLKL complex

4M69 の概要

• エントリーDOI: 10.2210/pdb4m69/pdb
• 関連するPDBエントリー: 4M66 4M68
• 分子名称: Receptor-interacting serine/threonine-protein kinase 3, Mixed lineage kinase domain-like protein, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (7 entities in total)
• 機能のキーワード: kinase, phosphorylation, transferase-signaling protein complex, transferase/signaling protein
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cytoplasm (Probable): Q9QZL0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67913.26

構造登録者

Xie, T.,Peng, W.,Yan, C.,Wu, J.,Shi, Y. (登録日: 2013-08-09, 公開日: 2013-10-16, 最終更新日: 2024-10-30)

主引用文献

Xie, T.,Peng, W.,Yan, C.,Wu, J.,Gong, X.,Shi, Y.
Structural Insights into RIP3-Mediated Necroptotic Signaling
Cell Rep, 5:70-78, 2013

PubMed Abstract: RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL functions as a substrate of RIP3 to mediate downstream signaling. The molecular mechanism by which RIP3 recognizes and phosphorylates MLKL remains unknown. Here, we report the crystal structures of the mouse RIP3 kinase domain, the MLKL kinase-like domain, and a binary complex between the two. Both RIP3 and MLKL adopt the canonical kinase fold. Free RIP3 exists in an active conformation, whereas MLKL-bound RIP3 is stabilized by AMP-PNP to adopt an inactive conformation. The formation of the RIP3-MLKL complex, involving their respective N- and C-lobes, is accompanied by pronounced conformational changes of the αC helix and activation loop in RIP3 and the corresponding structural elements in MLKL. RIP3-mediated MLKL phosphorylation, though important for downstream signaling, is dispensable for stable complex formation between RIP3 and MLKL. Our study serves as a framework for mechanistic understanding of RIP3-mediated necroptotic signaling.

PubMed: 24095729
DOI: 10.1016/j.celrep.2013.08.044

実験手法

X-RAY DIFFRACTION (2.497 Å)