2pom

OverviewOverview

In addition to caspase inhibition, X-linked inhibitor of apoptosis (XIAP), induces NF-kappaB and MAP kinase activation during TGF-b and BMP receptor, signaling and upon overexpression. Here we show that the BIR1 domain of, XIAP, which has no previously ascribed function, directly interacts with, TAB1 to induce NF-kappaB activation. TAB1 is an upstream adaptor for the, activation of the kinase TAK1, which in turn couples to the NF-kappaB, pathway. We report the crystal structures of BIR1, TAB1, and the BIR1/TAB1, complex. The BIR1/TAB1 structure reveals a striking butterfly-shaped dimer, and the detailed interaction between BIR1 and TAB1. Structure-based, mutagenesis and knockdown of TAB1 show unambiguously that the BIR1/TAB1, interaction is crucial for XIAP-induced TAK1 and NF-kappaB activation. We, show that although not interacting with BIR1, Smac, the antagonist for, caspase inhibition by XIAP, also inhibits the XIAP/TAB1 interaction., Disruption of BIR1 dimerization abolishes XIAP-mediated NF-kappaB, activation, implicating a proximity-induced mechanism for TAK1 activation.

About this StructureAbout this Structure

2POM is a Single protein structure of sequence from Homo sapiens with MN as ligand. Full crystallographic information is available from OCA.

ReferenceReference

XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization., Lu M, Lin SC, Huang Y, Kang YJ, Rich R, Lo YC, Myszka D, Han J, Wu H, Mol Cell. 2007 Jun 8;26(5):689-702. PMID:17560374

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