Structural highlights
Function
[CAR18_HUMAN] Inhibits generation of IL-1-beta by interacting with caspase-1 and preventing its association with RIP2. Down-regulates the release of IL1B.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
ProIL-1beta is a proinflammatory cytokine that is proteolytically processed to its active form by caspase-1. Upon receipt of a proinflammatory stimulus, an upstream adaptor, RIP2, binds and oligomerizes caspase-1 zymogen, promoting its autoactivation. ICEBERG is a novel protein that inhibits generation of IL-1beta by interacting with caspase-1 and preventing its association with RIP2. ICEBERG is induced by proinflammatory stimuli, suggesting that it may be part of a negative feedback loop. Consistent with this, enforced retroviral expression of ICEBERG inhibits lipopolysaccharide-induced IL-1beta generation. The structure of ICEBERG reveals it to be a member of the death-domain-fold superfamily. The distribution of surface charge is complementary to the homologous prodomain of caspase-1, suggesting that charge-charge interactions mediate binding of ICEBERG to the prodomain of caspase-1.
ICEBERG: a novel inhibitor of interleukin-1beta generation.,Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit VM Cell. 2000 Sep 29;103(1):99-111. PMID:11051551[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit VM. ICEBERG: a novel inhibitor of interleukin-1beta generation. Cell. 2000 Sep 29;103(1):99-111. PMID:11051551
- ↑ Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit VM. ICEBERG: a novel inhibitor of interleukin-1beta generation. Cell. 2000 Sep 29;103(1):99-111. PMID:11051551
