2poi
From Proteopedia
(New page: 200px<br /> <applet load="2poi" size="450" color="white" frame="true" align="right" spinBox="true" caption="2poi, resolution 1.800Å" /> '''Crystal structure ...) |
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| - | [[Image:2poi. | + | [[Image:2poi.jpg|left|200px]]<br /><applet load="2poi" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2poi" size=" | + | |
caption="2poi, resolution 1.800Å" /> | caption="2poi, resolution 1.800Å" /> | ||
'''Crystal structure of XIAP BIR1 domain (I222 form)'''<br /> | '''Crystal structure of XIAP BIR1 domain (I222 form)'''<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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Lymphoproliferative syndrome, X-linked, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300079 300079]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2POI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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:// | + | 2POI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=2POI 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 14:40:51 2008'' |
Revision as of 12:40, 23 January 2008
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Crystal structure of XIAP BIR1 domain (I222 form)
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.
About this Structure
2POI is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
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 Wed Jan 23 14:40:51 2008
Categories: Homo sapiens | Single protein | Lin, S. | ZN | Zinc finger
