2pop: Difference between revisions
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New page: left|200px<br /> <applet load="2pop" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pop, resolution 3.10Å" /> '''The Crystal Structu... |
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[[Image:2pop. | [[Image:2pop.jpg|left|200px]]<br /><applet load="2pop" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2pop" size=" | |||
caption="2pop, resolution 3.10Å" /> | caption="2pop, resolution 3.10Å" /> | ||
'''The Crystal Structure of TAB1 and BIR1 complex'''<br /> | '''The Crystal Structure of TAB1 and BIR1 complex'''<br /> | ||
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==Overview== | ==Overview== | ||
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. | 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 Structure== | ==About this Structure== | ||
2POP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2POP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2POP OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zinc finger]] | [[Category: zinc finger]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:40:58 2008'' | ||
