Crystal structure of the BIR1 domain of XIAP in two crystal forms.
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.
Lin
Su-Chang
SC
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.
Huang
Yihua
Y
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.
Lo
Yu-Chih
YC
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.
Lu
Miao
M
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.
Wu
Hao
H
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA. Electronic address: haowu@med.cornell.edu.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D018124:Receptors, Tumor Necrosis Factor; D016212:Transforming Growth Factor beta; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human
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