Map · Cell biology · Apoptosis

Apoptosis caspase cascade · cut after Asp

Programmed cell death is executed by proteases that cleave after aspartate. Initiators (8, 9) activate the executioner (3); granzyme B arrives from a killer cell. Same cut, different roles and different EC classes. Layer 2 of three — pick a machine. Real crystal coordinates (RCSB PDB).

The four proteases

INITIATOR · EXTRINSIC

Caspase-8 (death-receptor pathway)

Asp-Xaa cleaved at one site

Kicked off by death receptors. Cysteine protease that cuts its targets after an aspartate; activates caspase-3 downstream.

EC 3.4.22.61 · PDB 1QTN

▶ OPEN SIMULATOR

→

casp-3

INITIATOR · INTRINSIC

Caspase-9 (apoptosome pathway)

Asp-Xaa cleaved at one site

Triggered when cytochrome c (from the ETC) lets the apoptosome assemble. A Cys protease that cuts after Asp to start the cascade.

EC 3.4.22.62 · PDB 1JXQ

▶ OPEN SIMULATOR

→

casp-3

Caspase-3 (effector)

Asp-Xaa cleaved at one site

The main executioner: once the initiators switch it on, it cleaves the structural and repair proteins that dismantle the cell.

EC 3.4.22.56 · PDB 1CP3

▶ OPEN SIMULATOR

→

death

IMMUNE · SERINE PROTEASE

Granzyme B (from cytotoxic T cells)

Asp-Xaa cleaved at one site

Delivered by killer cells to trigger apoptosis in a target. Cleaves after Asp like a caspase, but it is a Ser protease with a different EC — same cut, different chemistry.

EC 3.4.21.79 · PDB 1IAU

▶ OPEN SIMULATOR

⤷ Role split, not chemical split: initiators (8, 9) and the executioner (3) share the Cys-after-Asp cut; granzyme B does the same cut with a Ser.