lecture 8 Flashcards
Microtubule motor proteins
Dynein and Kinesin
What do microtubule motor protein do?
Transport membrane bound vesicles, proteins and organelles at expense of ATP
What direction do kinesins move cargo?
(+) end of microtubule - anterograde
What direction do dyneins move cargo?
(-) end of microtubule - Retrograde
What does kinesin family domain contain?
- ATP binding site
- Microtubule binding site of motor
- Neck domain takes steps - connects motor domain to stalk domain
- Cargo binding domain
Kinesin 1
Globular, bulbous region at one end of molecule - region enlarged when antibody that binds to motor domain is present
- Head or feet hydrolyse ATP to generate energy for neck movement
- Has a stalk, tail and binding site in foot
Kinesin 1 cargo transport
- Each requires 1 ATP movement in neck
- Cargo binding site
- Anterograde
Describe the different kinesins types
Kinesin 1 (conventional) - 2 heads, stalks the same
Kinesin 2 (heterotrimeric) - head and stalks differ
Kinesin 5 (bipolar) - 4 head and stalks - sliding - mitosis to separate chromosomes
Kinesin 13 (KinI) - End disassembly
Describe the process of kinesin movement along microtubules
- Forward motor binds beta-tubulin, releasing ADP
- Forward head binds ATP
- Conformational change in neck linker causes rear head to swing forward
- New forward head releases ADP trailing head hydrolyses ATP and releases Pi
Catalytic core of kinesin is similar to catalytic core of what other molecule?
Myosin
Cytosolic dyneins
- Retrograde (transport cargo towards - end of microtubule)
- Very different structure to kinesins
- Do have ATPase and microtubule binding domains
- Linked to cargos by large complexes of microtubule binding proteins
Dynein structural components
- ATPase domain (head)
- Microtubule binding domain (stalk)
- Dynactin binding domain (Stem)
Dynactin
- Near domain hydrolyses ATP which generates a force
- Results in far mT binding domain detaching and moving forward one step
- Cargo binding domain - huge complex which includes dynamitin, CapZ, Arp1
- Required for cargo attachment
- P150glued - helps dynein attach to microtubule at start of transport process
What happens at the end of a microtubule?
- Motor proteins hitch a ride back with cargo of other motor proteins
- 600nm per second - centre to periphery of cell in 2-3 seconds
- Sciatic nerve over 1m long in some people - days rather than hours
Tau tangles
- Cause Alzheimer’s disease
- Microtubule disintegrates with subunits falling apart
- Causes tangled clumps of tau proteins