Overview
Apoptosis is a controlled form of cell death that uses caspases to dismantle cells in an organized way that supports tissue health.
Initiator Caspases
- Initiator caspases are proteins that start apoptosis.
- They are initially inactive, existing as single monomers called procaspases.
- Each initiator procaspase has:
- A protease domain at the carboxy-terminal region.
- A small adaptor-binding domain near the amino terminus.
- Apoptotic signals activate adaptor proteins that carry multiple binding sites.
- These adaptor proteins bind to the amino-terminal domains of initiator procaspases.
- Binding to adaptors brings procaspases together and causes their dimerization.
- Dimerization leads to cleavage at a specific site in the protease domains.
- This cleavage activates the initiator caspases.
- Each protease domain is then rearranged into a large subunit and a small subunit.
Executioner Caspases
- Executioner caspases exist as dimers but are initially inactive.
- Activated initiator caspases cleave the protease domains of executioner caspases.
- Cleavage causes a conformational change in the executioner dimers.
- This conformational change converts them into active executioner caspases.
- Active executioner caspases cleave many key cellular proteins.
- This extensive protein cleavage drives programmed cell death and supports normal cell turnover.
Caspase Activation Pathway (Summary Table)
| Component | Initial State | Activation Trigger | Activated Outcome |
|---|
| Initiator caspase | Inactive monomer (procaspase) | Binding to adaptor proteins after apoptotic signal | Dimerization, protease cleavage, rearrangement into two subunits |
| Adaptor protein | Inactive until signal | Apoptotic signal | Binds multiple initiator procaspases via amino-terminal domains |
| Executioner caspase | Inactive dimer | Cleavage by activated initiator caspases | Conformational change and activation |
| Cellular proteins | Intact, functional proteins | Cleavage by active executioner caspases | Degradation that produces programmed cell death |
Key Terms & Definitions
- Apoptosis: Controlled, programmed cell death that supports healthy tissues.
- Initiator caspases: Caspases that begin the apoptotic cascade when activated.
- Executioner caspases: Caspases that directly cleave key cellular proteins to kill the cell.
- Procaspase: Inactive precursor form of a caspase.
- Dimerization: Process where two protein molecules join to form a dimer.
- Protease domain: Region of a caspase that cleaves other proteins.
- Adaptor proteins: Proteins that bind procaspases and bring them together after an apoptotic signal.
- Conformational change: Structural change in a protein that alters its activity.
Action Items / Next Steps
- Review the sequence: apoptotic signal → adaptor binding → initiator activation → executioner activation → protein cleavage.
- Practice drawing a simple flow diagram of the caspase activation pathway.
- Memorize core terms: apoptosis, initiator caspase, executioner caspase, procaspase, adaptor protein.