Scholarlink

<p>Apoptosis in <i>Drosophila</i> is governed by caspases, inhibitor of apoptosis proteins (IAPs), and IAP antagonists. Using AlphaFold3, we modeled full-length 3D structures of the IAP antagonists Reaper, Hid, Grim, Sickle, and Jafrac2, as well as DIAP1 and dBruce, and their binary and higher-order complexes. We predict a paradoxical role for the N-terminal methionine of Reaper in stabilizing Reaper/Hid complexes and inhibiting DIAP1 binding. Our models reveal that Reaper uniquely engages both BIR1 and BIR2 domains of DIAP1, guided by α-helical residues in its backbone, while all other IAP antagonists preferentially target BIR2. Higher-order assemblies show how Reaper and Hid as well as Reaper and Grim cooperatively engage DIAP1 and allosterically modulate its E3 ligase activity. We present the first full-length model of dBruce and its inhibitory interaction with Rpr. These findings provide a comprehensive structural framework for apoptosis regulation in <i>Drosophila</i>, and offer new insights into conserved mechanisms of caspase control and IAP antagonism across species.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

AlphaFold3-based modeling uncovers the dynamic structural interface between full-length IAP antagonists and DIAP1 for apoptosis regulation in Drosophila

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月10日

查看全文
  • Pooja Rai,
  • Andreas Bergmann

摘要

Apoptosis in Drosophila is governed by caspases, inhibitor of apoptosis proteins (IAPs), and IAP antagonists. Using AlphaFold3, we modeled full-length 3D structures of the IAP antagonists Reaper, Hid, Grim, Sickle, and Jafrac2, as well as DIAP1 and dBruce, and their binary and higher-order complexes. We predict a paradoxical role for the N-terminal methionine of Reaper in stabilizing Reaper/Hid complexes and inhibiting DIAP1 binding. Our models reveal that Reaper uniquely engages both BIR1 and BIR2 domains of DIAP1, guided by α-helical residues in its backbone, while all other IAP antagonists preferentially target BIR2. Higher-order assemblies show how Reaper and Hid as well as Reaper and Grim cooperatively engage DIAP1 and allosterically modulate its E3 ligase activity. We present the first full-length model of dBruce and its inhibitory interaction with Rpr. These findings provide a comprehensive structural framework for apoptosis regulation in Drosophila, and offer new insights into conserved mechanisms of caspase control and IAP antagonism across species.