Abstract
It has been suggested that the Drosophila Hid protein interacts with the baculovirus Op-IAP protein in a manner similar to that of human Smac binding to XIAP, based largely on amino acid sequence homology. However, there is little direct experimental evidence in support of this hypothesis; indeed, evidence exists from previous studies suggesting that the mode of binding is not similar. We have now precisely mapped the interaction between Hid and Op-IAP, and we show clearly for the first time that the biochemical interactions between the amino terminus of Hid and BIR2 of Op-IAP are highly similar to those found between the processed amino terminus of Smac and BIR3 of XIAP. Also similar to Smac, the amino terminus of Hid must be processed to bind Op-IAP. In addition, our data also suggest that a second interaction between Hid and Op-IAP exists that does not involve the amino terminus of Hid, which may explain some of the earlier contradictory results. The evolutionary conservation of this mechanism of binding underscores its importance in apoptotic regulation. Nevertheless, interaction with Hid is not sufficient for Op-IAP to inhibit apoptosis induced by Hid overexpres. sion or by treatment with actinomycin D, indicating that additional sequence elements are required for the antiapoptotic function of Op-IAP.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2454-2462 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 277 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jan 25 2002 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Biochemistry
Cite this
Sequence requirements for hid binding and apoptosis regulation in the baculovirus inhibitor of apoptosis Op-IAP. Hid binds Op-IAP in a manner similar to Smac binding of XIAP. / Wright, Casey; Clem, Rollie J.
In: Journal of Biological Chemistry, Vol. 277, No. 4, 25.01.2002, p. 2454-2462.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sequence requirements for hid binding and apoptosis regulation in the baculovirus inhibitor of apoptosis Op-IAP. Hid binds Op-IAP in a manner similar to Smac binding of XIAP
AU - Wright, Casey
AU - Clem, Rollie J.
PY - 2002/1/25
Y1 - 2002/1/25
N2 - It has been suggested that the Drosophila Hid protein interacts with the baculovirus Op-IAP protein in a manner similar to that of human Smac binding to XIAP, based largely on amino acid sequence homology. However, there is little direct experimental evidence in support of this hypothesis; indeed, evidence exists from previous studies suggesting that the mode of binding is not similar. We have now precisely mapped the interaction between Hid and Op-IAP, and we show clearly for the first time that the biochemical interactions between the amino terminus of Hid and BIR2 of Op-IAP are highly similar to those found between the processed amino terminus of Smac and BIR3 of XIAP. Also similar to Smac, the amino terminus of Hid must be processed to bind Op-IAP. In addition, our data also suggest that a second interaction between Hid and Op-IAP exists that does not involve the amino terminus of Hid, which may explain some of the earlier contradictory results. The evolutionary conservation of this mechanism of binding underscores its importance in apoptotic regulation. Nevertheless, interaction with Hid is not sufficient for Op-IAP to inhibit apoptosis induced by Hid overexpres. sion or by treatment with actinomycin D, indicating that additional sequence elements are required for the antiapoptotic function of Op-IAP.
AB - It has been suggested that the Drosophila Hid protein interacts with the baculovirus Op-IAP protein in a manner similar to that of human Smac binding to XIAP, based largely on amino acid sequence homology. However, there is little direct experimental evidence in support of this hypothesis; indeed, evidence exists from previous studies suggesting that the mode of binding is not similar. We have now precisely mapped the interaction between Hid and Op-IAP, and we show clearly for the first time that the biochemical interactions between the amino terminus of Hid and BIR2 of Op-IAP are highly similar to those found between the processed amino terminus of Smac and BIR3 of XIAP. Also similar to Smac, the amino terminus of Hid must be processed to bind Op-IAP. In addition, our data also suggest that a second interaction between Hid and Op-IAP exists that does not involve the amino terminus of Hid, which may explain some of the earlier contradictory results. The evolutionary conservation of this mechanism of binding underscores its importance in apoptotic regulation. Nevertheless, interaction with Hid is not sufficient for Op-IAP to inhibit apoptosis induced by Hid overexpres. sion or by treatment with actinomycin D, indicating that additional sequence elements are required for the antiapoptotic function of Op-IAP.
UR - http://www.scopus.com/inward/record.url?scp=0037169556&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037169556&partnerID=8YFLogxK
U2 - 10.1074/jbc.M110500200
DO - 10.1074/jbc.M110500200
M3 - Article
C2 - 11717313
AN - SCOPUS:0037169556
VL - 277
SP - 2454
EP - 2462
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 4
ER -