Cell Reports volume 5, issue 1, P70-78 2013 DOI: 10.1016/j.celrep.2013.08.044 View full text
Tian Xie, Wei Peng, Chuangye Yan, Jianping Wu, Xinqi Gong, Yigong Shi

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 …

expand abstract