LECTURE 2 - MYOSIN Flashcards
What is myosin
Myosin is a motor protein that moves along actin filaments, using ATP as fuel.
It’s part of the cytoskeleton system and plays roles in muscle contraction, intracellular transport, and cell division.
There are ~40 different myosins in humans, and each has a different tail domain, which determines what it interacts with or where it functions.
What is the structure of myosin
Myosins are made up of one or two heavy chains (the motor subunits) and several light chains.
→ The heavy chains do the actual movement.
→ The light chains help stabilise and regulate the motor.
The head domains of all myosins are similar:
→ They bind to actin, bind and hydrolyze ATP, and generate force to move.
The tail domains of different myosins are different:
→ These determine what cellular structure or cargo the myosin interacts with, and therefore what its specific function is.
How Does Myosin Work?
Myosin hydrolyzes ATP (breaks it down into ADP + phosphate), which provides the energy needed to move.
This movement is often described as a “walking” or “power stroke” motion along actin filaments.
Diseases Linked to Myosin Mutations
Myosin II mutation ➝ Familial Hypertrophic Cardiomyopathy (FHC)
Myosin II is essential in heart muscle contraction.
A mutation in the MYH7 gene (which encodes myosin heavy chain) can cause FHC:
Heart muscle becomes abnormally thick (hypertrophied).
Can lead to sudden cardiac death, especially in young people with no prior symptoms.
This is often seen in athletes and may be the cause of unexpected collapses during intense activity.
How Myosin Interacts with Actin
- ATP Binding Causes Myosin to Release Actin
- ATP is then hydrolyzed (split into ADP + Pi), but these products remain bound to the myosin.
- ATP Hydrolysis Triggers a Conformational Change on myosin head, storing energy
- myosin-ADP-Pi complex binds to new actin site
- Pi Release Triggers the Power Stroke, pulling actin filament along, generating movement
- This cycle repeats: myosin keeps walking along the filament, converting chemical energy (ATP) into mechanical work (movement).
Step Size of Myosin Movement
Myosin II (e.g. in muscle) takes small steps: about 5–10 nm each.
Other myosins like Myosin V take much larger steps: up to 72 nm.
The step size depends on the length of the neck region of the myosin:
Longer neck = longer step (more leverage per cycle)
Roles of Myosin/Actin Interactions in Cells: Myosin V – Cargo Transport
- Myosin V has a longer neck than Myosin II
→ This allows for larger steps along the actin filament — useful for transport over longer distances. - It has globular cargo-binding domains at its tail
→ These allow binding to vesicles or organelles, so it can carry cargo within the cell. - Movement Mechanism:
The neck acts as a lever arm, amplifying the movement during each power stroke.
Myosin V walks in a hand-over-hand fashion — one head moves forward, then the other.
At least one head is always attached to the actin filament, ensuring stability during transport.
- Function:
→ Myosin V is specialized for intracellular transport, moving cargo like vesicles and organelles along actin tracks
Roles of Myosin/Actin Interactions in Cells: Myosin II – Muscle Contraction
- Function:
→ Myosin II is ideal for contractile roles, such as in muscle contraction, cytokinesis, or cell migration.
Structure
2. Myosin II forms bipolar filaments
→ These filaments allow many myosin molecules to pull actin filaments together, generating contractile force.
- Many heads work together:
→ Each head binds to actin only briefly (short “duty cycle”), but because there are so many of them, the actin is continuously engaged.
→ This cooperative action is efficient for generating quick, repeated contractions (e.g. in muscle).
- Adaptability:
→ This system is fast when moving light loads.
→ It can also produce stronger force when heavier loads are present by increasing the number of heads interacting with actin.
Structure of skeletal muscle
- highly organized tissue
- composed of bundles of muscle fibers called myofibers which contain several myofibrils.
- Myofibrils are composed of repeating units called sarcomeres - A and I band
- Bundles of myofibers form fascicles, and bundles of fascicles form muscle tissue.
What are myofibrils made up of
consist of bundles of protein filaments called myofilaments.
Myofibrils contain two types of myofilaments:
- thin filaments composed primarily of actin
- thick filaments composed primarily of myosin
Structure of A band and list the subdivisions
Where the thick (myosin) filaments and thin (actin) filaments overlap.
The thick filaments are located at the center of the sarcomere, within the A band.
Roughly the same length as the thick filaments.
Subdivisions of the A Band:
M Line
H Band
Zone of Overlap
Structure of A band: M line
Located in the center of the A band.
The M line proteins help link thick filaments together to stabilize their positions.
Structure of A band: H band
The H band is a lighter region on either side of the M line.
It only contains thick filaments and no thin filaments
Structure of A band: Zone of overlap
This is the dark region in the A band where the thin filaments overlap with the thick filaments.
In this zone, each thick filament is surrounded by three thin filaments, and each thin filament is surrounded by six thick filaments.
Structure of I band
The I band contains only thin filaments (actin) and no thick filaments.
It spans from the A band of one sarcomere to the A band of the next sarcomere.
The Z lines are in the middle of the I band and mark the boundary between two adjacent sarcomeres.
Muscle Contraction Cycle
- Ca²⁺ released into the sarcomere when muscle is stimulated, enters the zone of overlap
- Calcium binds to troponin on actin causing conformational change, which weakens the bond between troponin and tropomyosin
- Tropomyosin moves away from the active sites on actin, exposing the binding sites where the myosin heads can attach.
- energized myosin heads ( ADP and phosphate) attach to the exposed sites on the actin filaments, forming cross-bridge
- cross-bridge forming releases stored energy in the myosin head
- myosin head pivots toward the M line (center of the sarcomere), pulling the actin filament along with it (POWER STROKE)
- ADP and phosphate bound to the myosin head are released.
- After the power stroke, another molecule of ATP binds to the myosin head, breaking cross-bridge and re-exposing active site
