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'''The Crystal Structure of TAB1 and BIR1 complex''' | '''The Crystal Structure of TAB1 and BIR1 complex''' | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Lin, S C.]] | [[Category: Lin, S C.]] | ||
[[Category: | [[Category: Bir domain]] | ||
[[Category: | [[Category: Pp2c-like domain]] | ||
[[Category: | [[Category: Zinc finger]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:33:14 2008'' | |||
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Revision as of 13:33, 4 May 2008
The Crystal Structure of TAB1 and BIR1 complex
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
2POP is a Protein complex structure of sequences from Homo sapiens. 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 Page seeded by OCA on Sun May 4 13:33:14 2008