4BTF

Structure of MLKL

4BTF の概要

• エントリーDOI: 10.2210/pdb4btf/pdb
• 分子名称: MIXED LINEAGE KINASE DOMAIN-LIKE PROTEIN, FORMIC ACID, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: transferase, pseduokinase, necroptosis
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54026.95

構造登録者

Czabotar, P.E.,Murphy, J.M. (登録日: 2013-06-16, 公開日: 2013-09-18, 最終更新日: 2024-05-08)

主引用文献

Murphy, J.M.,Czabotar, P.E.,Hildebrand, J.M.,Lucet, I.S.,Zhang, J.-G.,Alvarez-Diaz, S.,Lewis, R.,Lalaoui, N.,Metcalf, D.,Webb, A.I.,Young, S.N.,Varghese, L.N.,Tannahill, G.M.,Hatchell, E.C.,Majewski, I.J.,Okamoto, T.,Dobson, R.C.J.,Hilton, D.J.,Babon, J.J.,Nicola, N.A.,Strasser, A.,Silke, J.,Alexander, W.S.
The Pseudokinase Mlkl Mediates Necroptosis Via a Molecular Switch Mechanism
Immunity, 39:443-, 2013

PubMed Abstract: Mixed lineage kinase domain-like (MLKL) is a component of the "necrosome," the multiprotein complex that triggers tumor necrosis factor (TNF)-induced cell death by necroptosis. To define the specific role and molecular mechanism of MLKL action, we generated MLKL-deficient mice and solved the crystal structure of MLKL. Although MLKL-deficient mice were viable and displayed no hematopoietic anomalies or other obvious pathology, cells derived from these animals were resistant to TNF-induced necroptosis unless MLKL expression was restored. Structurally, MLKL comprises a four-helical bundle tethered to the pseudokinase domain, which contains an unusual pseudoactive site. Although the pseudokinase domain binds ATP, it is catalytically inactive and its essential nonenzymatic role in necroptotic signaling is induced by receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated phosphorylation. Structure-guided mutation of the MLKL pseudoactive site resulted in constitutive, RIPK3-independent necroptosis, demonstrating that modification of MLKL is essential for propagation of the necroptosis pathway downstream of RIPK3.

PubMed: 24012422
DOI: 10.1016/J.IMMUNI.2013.06.018

実験手法

X-RAY DIFFRACTION (2.604 Å)