Caspases from scleractinian coral show unique regulatory features.
Caspases from scleractinian coral show unique regulatory features.
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石珊瑚的半胱天冬酶具有独特的调节功能。
DOI：
10.1074/jbc.ra120.014345
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发表时间：
2020-10-23
期刊：
影响因子：
--
通讯作者：
Clark AC
中科院分区：
文献类型：
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作者：
Shrestha S;Tung J;Grinshpon RD;Swartz P;Hamilton PT;Dimos B;Mydlarz L;Clark AC
珊瑚礁在地球仪各地正在急剧减少，珊瑚疾病和温度引起的白化是这些减少的主要驱动力。细胞凋亡的调控是珊瑚应激反应的重要组成部分。虽然已知刺胞动物含有复杂的细胞凋亡信号通路，类似于脊椎动物中的那些，但导致细胞死亡的机制在很大程度上尚未探索。我们确定并表征了两个半胱天冬酶，每一个从Orbicella faveolata，一种疾病敏感的造礁珊瑚，和Porites astreoides，一种抗病造礁珊瑚。预测的半胱天冬酶的同源物的人的执行者半胱天冬酶-3和-7，但OfCasp 3a（Orbicella faveolata半胱天冬酶-3a）和PaCasp 7a（Porites astreoides半胱天冬酶-7a），我们表明是DXXDases，含有一个N-末端半胱天冬酶激活/募集结构域（CARD）类似于人的启动子/炎症半胱天冬酶。OfCasp 3b（Orbicella faveolata caspase-3b）和PaCasp 3（Porites astreoides caspase-3），我们证明是VXXDases，具有短的前结构域，像人类刽子手caspase。我们的生化分析表明，珊瑚中的机制与人类不同，其中含有CARD的DXXDase在死亡平台上被激活，但蛋白酶不直接激活VXXDase。第一个X-射线晶体结构的珊瑚caspase，PaCasp 7a在1.57 μ m的分辨率确定，揭示了一个保守的折叠和N-末端肽结合附近的活性位点，可以作为一个监管exosite。在其他物种的起始半胱天冬酶中也观察到了结合口袋。这些结果提示了底物选择的进化机制，同时保持了CARD介导的二聚化的常见激活机制。
Coral reefs are experiencing precipitous declines around the globe with coral diseases and temperature-induced bleaching being primary drivers of these declines. Regulation of apoptotic cell death is an important component in the coral stress response. Although cnidaria are known to contain complex apoptotic signaling pathways, similar to those in vertebrates, the mechanisms leading to cell death are largely unexplored. We identified and characterized two caspases each from Orbicella faveolata, a disease-sensitive reef-building coral, and Porites astreoides, a disease-resistant reef-building coral. The caspases are predicted homologs of the human executioner caspases-3 and -7, but OfCasp3a (Orbicella faveolata caspase-3a) and PaCasp7a (Porites astreoides caspase-7a), which we show to be DXXDases, contain an N-terminal caspase activation/recruitment domain (CARD) similar to human initiator/inflammatory caspases. OfCasp3b (Orbicella faveolata caspase-3b) and PaCasp3 (Porites astreoides caspase-3), which we show to be VXXDases, have short pro-domains, like human executioner caspases. Our biochemical analyses suggest a mechanism in coral which differs from that of humans, where the CARD-containing DXXDase is activated on death platforms but the protease does not directly activate the VXXDase. The first X-ray crystal structure of a coral caspase, of PaCasp7a determined at 1.57 Å resolution, reveals a conserved fold and an N-terminal peptide bound near the active site that may serve as a regulatory exosite. The binding pocket has been observed in initiator caspases of other species. These results suggest mechanisms for the evolution of substrate selection while maintaining common activation mechanisms of CARD-mediated dimerization.