The inflammasome adaptor ASC induces procaspase-8 death effector domain filaments

Vajjhala, Parimala R., Lu, Alvin, Brown, Darren L., Pang, Siew Wai, Sagulenko, Vitaliya, Sester, David P., Cridland, Simon O., Hill, Justine M., Schroder, Kate, Stow, Jennifer L., Wu, Hao and Stacey, Katryn J. (2015) The inflammasome adaptor ASC induces procaspase-8 death effector domain filaments. Journal of Biological Chemistry, 290 49: 29217-29230. doi:10.1074/jbc.M115.687731

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Author Vajjhala, Parimala R.
Lu, Alvin
Brown, Darren L.
Pang, Siew Wai
Sagulenko, Vitaliya
Sester, David P.
Cridland, Simon O.
Hill, Justine M.
Schroder, Kate
Stow, Jennifer L.
Wu, Hao
Stacey, Katryn J.
Title The inflammasome adaptor ASC induces procaspase-8 death effector domain filaments
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 1083-351X
Publication date 2015-12-04
Sub-type Article (original research)
DOI 10.1074/jbc.M115.687731
Open Access Status File (Publisher version)
Volume 290
Issue 49
Start page 29217
End page 29230
Total pages 14
Place of publication Rockville, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2016
Language eng
Abstract Inflammasomes mediate inflammatory and cell death responses to pathogens and cellular stress signals via activation of procaspases-1 and -8. During inflammasome assembly, activated receptors of the NLR or PYHIN family recruit the adaptor protein ASC and initiate polymerisation of its pyrin domain (PYD) into filaments. We show that ASC filaments in turn nucleate procaspase-8 death effector domain (DED) filaments in vitro and in vivo. Interaction between ASC PYD and procaspase-8 tandem DEDs optimally required both DEDs, and represents an unusual heterotypic interaction between domains of the death-fold superfamily. Analysis of ASC PYD mutants showed that interaction surfaces that mediate procaspase-8 interaction overlap with those required for ASC self-association and interaction with the PYDs of inflammasome initiators. Our data indicate that multiple types of death-fold domain filaments form at inflammasomes and that PYD/DED and homotypic PYD interaction modes are similar. Interestingly, we observed condensation of procaspase-8 filaments containing the catalytic domain, suggesting that procaspase-8 interactions within and/or between filaments may be involved in caspase-8 activation. Procaspase-8 filaments may also be relevant to apoptosis induced by death receptors.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Dec 2015, 11:07:15 EST by Susan Allen on behalf of Institute for Molecular Bioscience