An update on card only proteins (COPS) and pyd only proteins (POPS) as inflammasome regulators

Savita Devi, Christian Stehlik*, Andrea Dorfleutner

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Inflammasomes are protein scaffolds required for the activation of caspase-1 and the subsequent release of interleukin (IL)-1β, IL-18, and danger signals, as well as the induction of pyroptotic cell death to restore homeostasis following infection and sterile tissue damage. However, excessive inflammasome activation also causes detrimental inflammatory disease. Therefore, extensive control mechanisms are necessary to prevent improper inflammasome responses and inflammatory disease. Inflammasomes are assembled by sequential nucleated polymerization of Pyrin domain (PYD) and caspase recruitment domain (CARD)-containing inflammasome components. Once polymerization is nucleated, this process proceeds in a self-perpetuating manner and represents a point of no return. Therefore, regulation of this key step is crucial for a controlled inflammasome response. Here, we provide an update on two single domain protein families containing either a PYD or a CARD, the PYD-only proteins (POPs) and CARD-only proteins (COPs), respectively. Their structure allows them to occupy and block access to key protein–protein interaction domains necessary for inflammasome assembly, thereby regulating the threshold of these nucleated polymerization events, and consequently, the inflammatory host response.

Original languageEnglish (US)
Article number6901
Pages (from-to)1-18
Number of pages18
JournalInternational journal of molecular sciences
Volume21
Issue number18
DOIs
StatePublished - Sep 2 2020
Externally publishedYes

Keywords

  • AIM2 like receptor
  • ALR
  • ASC
  • CARD
  • COP
  • Caspase recruitment domain
  • Caspase-1
  • Inflammasome
  • Interleukin-1
  • NLR
  • Nod-like receptor
  • POP
  • PYD
  • PYRIN domain

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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