2POI

Crystal structure of XIAP BIR1 domain (I222 form)

Summary for 2POI

• Entry DOI: 10.2210/pdb2poi/pdb
• Descriptor: Baculoviral IAP repeat-containing protein 4, ZINC ION (3 entities in total)
• Functional Keywords: zinc finger, signaling protein-apoptosis complex, signaling protein/apoptosis
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P98170
• Total number of polymer chains: 1
• Total formula weight: 10563.12

Authors

Lin, S. (deposition date: 2007-04-26, release date: 2007-07-03, Last modification date: 2024-02-21)

Primary citation

Lu, M.,Lin, S.C.,Huang, Y.,Kang, Y.J.,Rich, R.,Lo, Y.C.,Myszka, D.,Han, J.,Wu, H.
XIAP Induces NF-kappaB Activation via the BIR1/TAB1 Interaction and BIR1 Dimerization.
Mol.Cell, 26:689-702, 2007

PubMed Abstract: 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.

PubMed: 17560374
DOI: 10.1016/j.molcel.2007.05.006

Experimental method

X-RAY DIFFRACTION (1.8 Å)