Procaspase 9 forms dimer

CASP9 is normally present as an inactive monomeric propeptide (procaspase‑9 or zymogen). Upon apoptosis, the N‑terminal caspase recruitment domain (CARD) of procaspase‑9 binds to the exposed CARD of the apoptotic protease‑activating factor‑1 (APAF1) through homotypic interactions (Qin H et al. 1999). Procaspase-9 has been estimated to bind to the apoptosome with ratios between 2–5 zymogens per 7 APAF:cytochrome c (CYCS) molecules (Cheng TC et al. 2016). The function of the apoptosome is to promote homodimerization of CASP9 (Jiang X and Wang X 2000; Srinivasula SM et al. 2001; Shiozaki EN et al. 2002). While activation of CASP9 involves dimerization, proteolytic cleavage of CASP9 may not be required. The unprocessed CASP9 exhibited high catalytic activity (Renatus et al. 2001; Acehan D et al. 2002). Furthermore, unlike other initiator caspases, including caspases‑2, ‑8 and ‑10, the prodomain of CASP9 is not removed during apoptosis; in fact, CASP9 (in both its procaspase‑9 and processed forms) must remain bound to the apoptosome to retain substantial catalytic activity (Bratton et al. 2001; Rodriguez and Lazebnik 1999). Once activated in the apoptosome, CASP9 dimer cleaves and activates procaspase‑3 and ‑7.

CASP9通常以非活性单聚前肽（前caspase-9或酶原）的形式存在。在细胞凋亡过程中，前caspase-9的N端caspase募集结构域（CARD）通过同源相互作用（Qin H et al. 1999）与暴露的凋亡蛋白酶活化因子-1（APAF1）的CARD结合。据估计，前caspase-9与凋亡体的结合比例为每7个APAF1：细胞色素c（CYCS）分子，存在2～5个酶原（Cheng TC et al. 2016）。凋亡体的功能在于促进CASP9的同源二聚化（Jiang X and Wang X 2000；Srinivasula SM et al. 2001；Shiozaki EN et al. 2002）。虽然CASP9的激活涉及二聚化，但其蛋白酶解切割可能并非必需。未经处理的CASP9展现出高催化活性（Renatus et al. 2001；Acehan D et al. 2002）。此外，与caspase-2、-8和-10等其他启动子caspase不同，CASP9的前结构域在细胞凋亡过程中并未被去除；事实上，CASP9（无论是前caspase-9还是其处理形式）必须保持与凋亡体的结合以维持显著的催化活性（Bratton et al. 2001；Rodriguez and Lazebnik 1999）。一旦在凋亡体中被激活，CASP9的二聚体将切割并激活前caspase-3和-7。