Denault Jean-Bernard, Békés Miklós, Scott Fiona L, Sexton Kelly M B, Bogyo Matthew, Salvesen Guy S
The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Mol Cell. 2006 Aug;23(4):523-33. doi: 10.1016/j.molcel.2006.06.020.
Caspase-7 is an obligate dimer of catalytic domains, with generation of activity requiring limited proteolysis within a region that separates the large and small chains of each domain. Using hybrid dimers we distinguish the relative contribution of each domain to catalysis by the whole molecule. We demonstrate that the zymogen arises from direct dimerization and not domain swapping. In contrast to previous conclusions, we show that only one of the catalytic domains must be proteolyzed to enable activation. The processed domain of this singly cleaved zymogen has the same catalytic activity as a domain of fully active caspase-7. A transient intermediate of singly cleaved dimeric caspase-7 can be found in a cell-free model of apoptosis induction. However, we see no evidence for an analogous intermediate of the related executioner caspase-3. Our study demonstrates the efficiency by which the executioner caspases are activated in vivo.
半胱天冬酶-7是催化结构域的 obligate 二聚体，其活性的产生需要在分隔每个结构域的大链和小链的区域内进行有限的蛋白水解。使用杂合二聚体，我们区分了每个结构域对整个分子催化的相对贡献。我们证明酶原源于直接二聚化而非结构域交换。与先前的结论相反，我们表明只需对其中一个催化结构域进行蛋白水解就能实现激活。这种单切割酶原的加工结构域具有与完全活性的半胱天冬酶-7的一个结构域相同的催化活性。在无细胞凋亡诱导模型中可以发现单切割二聚体半胱天冬酶-7的瞬时中间体。然而，我们没有发现相关刽子手半胱天冬酶-3存在类似中间体的证据。我们的研究证明了刽子手半胱天冬酶在体内被激活的效率。
