Lecture 6.5 - Myosin

Question 1

What is myosin function?

Answer 1

All myosin’s use energy derived from ATP hydrolysis to “walk” along actin filaments
* Contraction
* Transport of specific cellular components
All myosin’s are composed of one or two heavy chains and several light chains. The heavy chains have similar head domains which interact with actin. The tail domains of different actin’s are different.

There are roughly 40 different human myosin’s known - mutations in some myosin’s can cause diseases
E.g. mutation in myosin II can cause familial hypertrophic Cardiomyopathy.

Question 2

Descrive myosin movement.

In muscle contraction

Answer 2

1. Myosin binds ATP and the head is released from the actin filament
   
   2. Hydrolysis of ATP to ADP and phosphate rotates myosin head into high energy state
   3. Myosin binds to the actin filament
   4. Release of P and elastic energy straightens myosin and moves the actin filament to the left
      ADP released, ATP bound and head released form actin
      The size of the step depends on the length of the neck region. The longer the neck the longer the step

Class Step Size Function
I 10-14 nm Membrane association and endocytosis
II 5-10 nm Contraction
V 36 nm Organelle transport

* Myosin proteins have a longer neck than myosin II
* Myosin II proteins can assemble into bipolar filaments involved in contractile functions
* Myosin V also has globular cargo binding domains at its tail

Question 3

Describe how myosin V moves cargo along filaments.

Answer 3

The neck domain acts as a lever arm for the conformational change
At any time during the cycle one or both of the heads are bound to the actin filament
As myosin V moves down a filament its two heads follow a hand over hand movement. The longer cycle and large step size correspond with the function of myosin V which is to provide the motor to move cargo along actin filaments

Question 4

How is myosin II adapted for its function?

Answer 4

Bipolar complexes of myosin II work together in contraction. Each head remains bound only transiently while other heads bind and move the filament which allows for fast movement and the flexibility of greater force for heavier loads.
Titin stabilises the myosin and holds it in place

Question 5

How does calcium concentration impact muscle contraction?

Answer 5

The mechanism by which a rise in ca2+ triggers contractions differs in skeletal and smooth muscle. Binding of Ca2+ to troponin C leads to muscle contraction as myosin binding sites made accessible. Contraction of smooth muscle is triggered by activation of myosin light-chain kinase by Ca2+ - calmodulin.

Question 6

What are contractile bundles in non-muscle cells.

Answer 6

The contractile ring generates the cleavage furrow during cytokinesis consists of actin filaments and myosin. A new generation of drugs called Rho-kinase inhibitors are being used to treat some cytoskeletal related diseases by influencing how leaky junctions are
Ripasudil a rho-kinase inhibitor- recently approved for the treatment of glaucoma - increases the outflow of aqueous humour by disrupting the actin cytoskeleton