The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In particular, CASP8 maturation involves a cascade of events initiated by the binding of CASP8 to FADD at the DISC.”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [291]
In the citing paper
“This interaction enables the assembly of a linear filament of CASP8 molecules (depending on their DEDs) that facilitates homodimerization and consequent activation by autoproteolytic cleavage [291–295].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [291]
Citations
Cites
SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information
Biasini, M., Bienert, S., Waterhouse, A. M., Arnold, K., Studer, G., Schmidt, T., Kiefer, F., Cassarino, T. G., Bertoni, M., Bordoli, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku340 · Cited by 4,709
The TNF and TNF Receptor Superfamilies
Locksley, R. M., Killeen, N., & Lenardo, M. J. (2001) · Cell · doi:10.1016/s0092-8674(01)00237-9 · Cited by 3,650
Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
Micheau, O., & Tschopp, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00521-x · Cited by 2,738
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., & Fitzgerald, K. A. (2009) · Nature · doi:10.1038/nature07725 · Cited by 2,627
Kischkel, F. C., Hellbardt, S., Behrmann, I., Germer, M., Pawlita, M., Krammer, P. H., & Peter, M. E. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00245.x · Cited by 2,181
Unified Polymerization Mechanism for the Assembly of ASC-Dependent Inflammasomes
Lu, A., Magupalli, V. G., Ruan, J., Yin, Q., Atianand, M. K., Vos, M. R., Schröder, G. F., Fitzgerald, K. A., Wu, H., & Egelman, E. H. (2014) · Cell · doi:10.1016/j.cell.2014.02.008 · Cited by 1,353
Self-citationHelical Assembly in the MyD88-IRAK4-IRAK2 Complex in TLR/IL-1R Signalling
Lin, S.-C., Lo, Y.-C., & Wu, H. (2010) · Nature · doi:10.1038/nature09121 · Cited by 1,111
Self-citationA Unified Model for Apical Caspase Activation
Boatright, K. M., Renatus, M., Scott, F. L., Sperandio, S., Shin, H., Pedersen, I. M., Ricci, J., Edris, W. A., Sutherlin, D. P., Green, D. R., et al. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00051-0 · Cited by 986
The many roles of FAS receptor signaling in the immune system
Strasser, A., Jost, P. J., & Nagata, S. (2009) · Immunity · doi:10.1016/j.immuni.2009.01.001 · Cited by 968
Feoktistova, M., Geserick, P., Kellert, B., Panayotova‐Dimitrova, D., Langlais, C., Hupe, M., Cain, K., MacFarlane, M., Häcker, G. A., & Leverkus, M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.011 · Cited by 878
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Newton, K., Strasser, A., Kayagaki, N., & Dixit, V. M. (2024) · Cell · doi:10.1016/j.cell.2023.11.044 · Cited by 1,068
Caspase‐8: regulating life and death
Tummers, B., & Green, D. R. (2017) · Immunological Reviews · doi:10.1111/imr.12541 · Cited by 779
Samir, P., Malireddi, R. K. S., & Kanneganti, T.-D. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00238 · Cited by 557
Wang, Y., & Kanneganti, T.-D. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.07.038 · Cited by 545
Metadata
- Authors
- 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.
- Affiliations
- Boston Children's Hospital (US)
- Howard Hughes Medical Institute (US)
- The University of Queensland (AU)
- National Institutes of Health (US)
- University of Washington (US)
- Texas Medical Center (US)
- University of Virginia (US)
- Corresponding author
- Wu, Hao
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 64
- Issue
- 2
- Pages
- 236-250
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5089849
- OpenAlex
- W2531084658
- Cited by
- 196
- References
- 48
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 24 · 2023: 9 · 2022: 16 · 2021: 35 · 2020: 25 · 2019: 24 · 2018: 13 · 2017: 10 · 2016: 1
- FWCI
- 8.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Health and Medical Research Council
- National Medical Research Council
- National Institute of General Medical Sciences (R01GM060635)
- National Institute of Allergy and Infectious Diseases (R37AI050872, R01AI045937, R01AI124491)
- National Institute of Biomedical Imaging and Bioengineering (R01EB001567)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (DP1HD087988)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- caspase-8, death-inducing signaling complex, FADD, c-FLIP, ASC, inflammasome, death receptor signaling, caspase activation, protein filament assembly, protein-protein interfaces, Fas-mediated apoptosis, caspase inhibition
- MeSH terms
- Death Effector Domain, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Amino Acid Sequence, Binding Sites, Cytoskeletal Proteins, Humans, Plasmids, Protein Binding, Recombinant Fusion Proteins, Transfection, Viral Proteins, Gene Expression, Sequence Alignment, Apoptosis, Sequence Homology, Amino Acid, fas Receptor, Jurkat Cells, Cryoelectron Microscopy, Caspase 8, Fas-Associated Death Domain Protein, Death Domain Receptor Signaling Adaptor Proteins, CASP8 and FADD-Like Apoptosis Regulating Protein, CARD Signaling Adaptor Proteins, Protein Interaction Domains and Motifs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
