4M69

Crystal structure of the mouse RIP3-MLKL complex

Summary for 4M69

• Entry DOI: 10.2210/pdb4m69/pdb
• Related: 4M66 4M68
• Descriptor: Receptor-interacting serine/threonine-protein kinase 3, Mixed lineage kinase domain-like protein, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (7 entities in total)
• Functional Keywords: kinase, phosphorylation, transferase-signaling protein complex, transferase/signaling protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm (Probable): Q9QZL0
• Total number of polymer chains: 2
• Total formula weight: 67913.26

Authors

Xie, T.,Peng, W.,Yan, C.,Wu, J.,Shi, Y. (deposition date: 2013-08-09, release date: 2013-10-16, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.497 Å)