5JQE

Crystal structure of caspase8 tDED

Summary for 5JQE

• Entry DOI: 10.2210/pdb5jqe/pdb
• Descriptor: Sugar ABC transporter substrate-binding protein,Caspase-8 chimera (1 entity in total)
• Functional Keywords: apoptosis, hydrolase
• Biological source: Escherichia coli, Homo sapiens (Human)
• Cellular location: Cytoplasm: Q14790
• Total number of polymer chains: 1
• Total formula weight: 63706.39

Authors

Fu, T.,Li, Y.,Lu, A.,Wu, H. (deposition date: 2016-05-04, release date: 2016-10-26, Last modification date: 2024-04-03)

Primary citation

Fu, T.M.,Li, Y.,Lu, A.,Li, Z.,Vajjhala, P.R.,Cruz, A.C.,Srivastava, D.B.,DiMaio, F.,Penczek, P.A.,Siegel, R.M.,Stacey, K.J.,Egelman, E.H.,Wu, H.
Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex.
Mol. Cell, 64:236-250, 2016

PubMed Abstract: Caspase-8 activation can be triggered by death receptor-mediated formation of the death-inducing signaling complex (DISC) and by the inflammasome adaptor ASC. Caspase-8 assembles with FADD at the DISC and with ASC at the inflammasome through its tandem death effector domain (tDED), which is regulated by the tDED-containing cellular inhibitor cFLIP and the viral inhibitor MC159. Here we present the caspase-8 tDED filament structure determined by cryoelectron microscopy. Extensive assembly interfaces not predicted by the previously proposed linear DED chain model were uncovered, and were further confirmed by structure-based mutagenesis in filament formation in vitro and Fas-induced apoptosis and ASC-mediated caspase-8 recruitment in cells. Structurally, the two DEDs in caspase-8 use quasi-equivalent contacts to enable assembly. Using the tDED filament structure as a template, structural analyses reveal the interaction surfaces between FADD and caspase-8 and the distinct mechanisms of regulation by cFLIP and MC159 through comingling and capping, respectively.

PubMed: 27746017
DOI: 10.1016/j.molcel.2016.09.009

Experimental method

X-RAY DIFFRACTION (3.157 Å)