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1dgn

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PDB ID 1dgn

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SOLUTION STRUCTURE OF ICEBERG, AN INHIBITOR OF INTERLEUKIN-1BETA GENERATION


Overview

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.

About this Structure

1DGN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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