Cell Death (Unit 7) Flashcards
Why are caspases zymogens
Zymogens are proteins with inactive enzymes
Capases need to be activated to work
What’s one way that caspases activate apoptosis
Inactivation of flippase and activation of scramblase
(both via cleavage)
How are initiator caspases activated?
Procaspases Brought into close proximity and then they permanently cleave eachother
What is meant by the fact that caspases cleave themselves?
They do autocatalysis and cleave other capases
What are the targets of executioner caspases?
Lamins, proteins that keep endonucleases inactive, cytolskletal compoents, cell-cell adhesion components
What binds to caspases to keep them inactive?
An adaptor protein (the prodomain)
Are caspases dimers or monomers?
Starts as one protein
Cleaved into large and small subunits to form heterodimer.
Active form consists of tetramer made from two heterodimers
What is the main way that all apop programs converge?
Caspase activation
What are caspases (based on name)
Proteases with a cysteine
Do caspases only do PCD?
Most do but some also do inflammation or immune response
How do caspases know where to cleave?
Look for signature tetrapeptide motif and cleave after the D (Asp)
What is caspase amplification?
One intiator caspase can activate multiple executioners
When can you no longer turn back apop?
Once executioners are activated
What is the apoptosome?
A wheel-like heptamer that activates initiator caspases
How is the apoptosome formed?
Released CytC (and dATP) binds Apaf1 to induce a shape change which frees its oligomerization domain and its CARD
7 active Apaf1s oligomerize into a wheel with CARD at the middle
It then recruits initiator caspases and activates them
Then, the initatior caspases(now on the wheel) activate executioners
What starts the instrinsic pathway?
Release of proteins meant to be in IMS
Release of CytC