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Title: Crystal Structure of the BIR1 Domain of XIAP in Two Crystal Forms

Abstract

X-linked inhibitor of apoptosis (XIAP) is a potent negative regulator of apoptosis. It also plays a role in BMP signaling, TGF-{beta} signaling, and copper homeostasis. Previous structural studies have shown that the baculoviral IAP repeat (BIR2 and BIR3) domains of XIAP interact with the IAP-binding-motifs (IBM) in several apoptosis proteins such as Smac and caspase-9 via the conserved IBM-binding groove. Here, we report the crystal structure in two crystal forms of the BIR1 domain of XIAP, which does not possess this IBM-binding groove and cannot interact with Smac or caspase-9. Instead, the BIR1 domain forms a conserved dimer through the region corresponding to the IBM-binding groove. Structural and sequence analyses suggest that this dimerization of BIR1 in XIAP may be conserved in other IAP family members such as cIAP1 and cIAP2 and may be important for the action of XIAP in TGF-{beta} and BMP signaling and the action of cIAP1 and cIAP2 in TNF receptor signaling.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930038
Report Number(s):
BNL-80659-2008-JA
Journal ID: ISSN 0022-2836; JMOBAK; TRN: US200822%%1272
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Molecular Biology; Journal Volume: 372
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; APOPTOSIS; COPPER; CRYSTAL STRUCTURE; CRYSTALS; DIMERIZATION; DIMERS; HOMEOSTASIS; PROTEINS; RECEPTORS; national synchrotron light source

Citation Formats

Lin,S., Huang, Y., Lo, Y., Lu, M., and Wu, H. Crystal Structure of the BIR1 Domain of XIAP in Two Crystal Forms. United States: N. p., 2007. Web. doi:10.1016/j.jmb.2007.07.019.
Lin,S., Huang, Y., Lo, Y., Lu, M., & Wu, H. Crystal Structure of the BIR1 Domain of XIAP in Two Crystal Forms. United States. doi:10.1016/j.jmb.2007.07.019.
Lin,S., Huang, Y., Lo, Y., Lu, M., and Wu, H. Mon . "Crystal Structure of the BIR1 Domain of XIAP in Two Crystal Forms". United States. doi:10.1016/j.jmb.2007.07.019.
@article{osti_930038,
title = {Crystal Structure of the BIR1 Domain of XIAP in Two Crystal Forms},
author = {Lin,S. and Huang, Y. and Lo, Y. and Lu, M. and Wu, H.},
abstractNote = {X-linked inhibitor of apoptosis (XIAP) is a potent negative regulator of apoptosis. It also plays a role in BMP signaling, TGF-{beta} signaling, and copper homeostasis. Previous structural studies have shown that the baculoviral IAP repeat (BIR2 and BIR3) domains of XIAP interact with the IAP-binding-motifs (IBM) in several apoptosis proteins such as Smac and caspase-9 via the conserved IBM-binding groove. Here, we report the crystal structure in two crystal forms of the BIR1 domain of XIAP, which does not possess this IBM-binding groove and cannot interact with Smac or caspase-9. Instead, the BIR1 domain forms a conserved dimer through the region corresponding to the IBM-binding groove. Structural and sequence analyses suggest that this dimerization of BIR1 in XIAP may be conserved in other IAP family members such as cIAP1 and cIAP2 and may be important for the action of XIAP in TGF-{beta} and BMP signaling and the action of cIAP1 and cIAP2 in TNF receptor signaling.},
doi = {10.1016/j.jmb.2007.07.019},
journal = {Journal of Molecular Biology},
number = ,
volume = 372,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}