LECTURE 4 - microtuble motor proteins and IFs Flashcards
What Are Microtubule Motor Proteins?
Motor proteins are specialized molecules that move along microtubules — long, tube-like structures inside cells.
They transport cargo (like vesicles, proteins, or organelles).
They use energy from ATP to “walk” along microtubules.
There are two main families:
Kinesins – usually move toward the plus end (cell periphery).
Dyneins – usually move toward the minus end (cell center).
Describe Kinesins
Direction: Most kinesins move cargo toward the (+) end of microtubules — this is called anterograde transport.
Motor Domain:
Located in the globular “bulbous” region at one end.
Contains the ATP binding site and microtubule binding site.
Responsible for movement, but not direction — directionality is controlled by the neck region.
Describe Kinesin 1
Structure of Kinesin-1:
A dimer of two heavy chains arranged in parallel.
Motor domains are found only at one end.
Movement mechanism:
The forward motor head binds β-tubulin and releases ADP.
ATP binding causes a conformational change in the neck linker, swinging the rear head forward.
The new forward head binds and releases ADP.
The trailing head hydrolyzes ATP, releasing Pi and detaching.
Describe kinesin 5
Kinesin 5 is a bipolar kinesin with motor domains on both ends.
Important in spindle dynamics during mitosis.
Describe dynein moto proteins
Direction of movement:
➤ Move towards the (−) end of microtubules (retrograde transport)
Function:
➤ Use ATP hydrolysis to generate force for movement
➤ Involved in cargo transport, organelle positioning, and cilia/flagella motion
Structure:
➤ Structurally different from kinesins, but still contain:
* ATPase domains
* Microtubule-binding domains
Describe Cytoplasmic Dynein (aka cytosolic dynein)
Function:
➤ Transports membrane-bound vesicles, organelles, and proteins in the cytoplasm
➤ Critical for retrograde transport in neurons and other cells
Cargo interaction:
➤ Dynein binds to cargo indirectly via the dynactin complex (a large multi-protein adapter)
Location:
➤ Found throughout the cytoplasm of cells
Explain Axonemal Dynein
Function:
➤ Drives movement of cilia and flagella by causing bending of the axoneme
Location:
➤ Found in the axoneme – the core structure of cilia and flagella
* Made of 9 outer microtubule doublets and 2 central microtubules (the 9+2 arrangement)
Mechanism:
➤ Axonemal dyneins generate sliding between microtubule doublets
➤ This sliding is converted into bending because of cross-linking proteins like nexin
* These proteins restrict free sliding, forcing a bend that results in motion
Basic Structure and Function of Intermediate Filaments (IFs)
Composition:
➤ Formed from a family of related proteins (e.g. keratin, lamin)
➤ No motor proteins involved
General structure:
➤ Assemble into strong, ropelike polymers
➤ Size: 10–12 nm in diameter (intermediate in size between actin and microtubules)
➤ Each subunit has a central α-helical rod domain flanked by globular N- and C-terminal domains
Assembly hierarchy:
➤ Subunits form dimers via coiled-coil interactions
➤ Dimers → tetramers → Protofilaments→ Protofibrils → Filament
Function:
➤ Provide mechanical support for the plasma membrane and nuclear envelope
➤ Key for cell adhesion and resisting mechanical stress
List the Five Major Classes of Intermediate Filaments
Class I & II: Keratins
Class III: Vimentin-like IFs
Class IV: Neurofilaments
Class V: Lamins
Class VI: Nestin
Describe Class I & II: Keratins
➤ Found in epithelial cells
➤ Provide tensile strength to skin, hair, nails
➤ Mutations → Epidermolysis bullosa simplex (blistering skin disorder)
Describe Class III: Vimentin-like IFs
➤ Include vimentin, desmin, and GFAP
➤ Found in mesenchymal cells, muscle, and glial cells respectively
Describe Class IV: Neurofilaments
➤ Found in neurons
➤ Important for axon diameter and nerve conduction speed
Describe Class V: Lamins
➤ Found in the nuclear envelope of all animal cells
➤ Help maintain nuclear shape and integrity
Describe Class VI: Nestin
➤ Expressed in neural stem cells
➤ Used as a marker for undifferentiated cells
Tissue/Cell Specificity of IFs
➤ IFs vary depending on the cell type, allowing them to serve as cell-specific markers
➤ Example: Corneal stem cells can be identified using immunolabelling for specific keratins
Stability of IFs
➤ More stable than actin filaments or microtubules
➤ Stability is due to the extensive overlapping of the rod domains forming a tough rope-like structure
IFAPs (Intermediate Filament Associated Proteins)
assist in filament organization and interactions with other cell components
describe a disease caused by a mutation in IFs
Epidermolysis bullosa simplex
makes the skin flake away from death of basal cells.
Without the normal bundles of keratin (defects in keratin 14), the cells become very fragile causing blistering and ‘butterfly skin’.
So keratin is important in maintaining epithelial structure by enforcing connections between cells.
